THE ~RSITY OF NEW MEXICOCOLLEGE OF PHARMACY

ALBUQUERQUE, NEW MEXICO

The University of New Mexico

Correspondence Continuing Education Coursesfor

Nuclear Pharmacists and Nuclear Medicine Professionals

VOLUMEIV, NUMBER 2

Factors to ConsiderMen Selecting Radiopharmaceutical Dosages

for Diagnostic Procedures

by:

Susan J. Ballinger, M. S., R.Ph., CNMT, BCNP

Co-sponsored by: ➤~mersham HEALTHCARE

H me Univemity of New Mefim College of ~ k approved by b &ti Councif m ~tid Mucntim M

a provider of co- pharmaccutiml cducntion. Program No. 039-W95-0fJ3-HM. 2.5 C~ Hours or .25 C~’U

m

Editor

and

Director of Pharmacy Coti”nw”ng Wuc&n

William B. Hladik III, M. S., R.Ph.College of Pharmacy

University of New Mexiw

Associate -or

and

Produ&”on Specialkt

Sharon I. Ramirez, Staff AssistantCollege of Pharmacy

University of New Mexico

Whiletheadviceandinformationinthtipublicationarebehevcdto betrueandaccurateatpresstime,neither the author(s) northe editor nor the publisher can aec~t any legal responsibility for any errors or omissions that may be made. The publisherm~es no warranty, exp=s or implied, with res~t to the ma~rial mntaind herein.

Copyright 1995Universityof New Mexico

PharmacyContintig Education

FACTORS TO CONSIDER WHEN SELECTINGRADIOPHARMAC EUTICAL DOSAGES

FORDIAGNOSTIC PROCEDURES

By

SUSAN J. BALLINGER, M. S,, R.Ph., CNMT, BCNP

STATEMENT OF OBJECTIVES

The purpose of this correspondence lesson is to increase the reader’s knowledge of general dosing requirementsfor various nuclear medicine studies for adult and pediatric patients. The reader should be able to discuss,calculate and understand these dosing requirements.

Upon successful completion of this material, the reader should be able to:

1.

2.

●3.

4.

5.

6.

7.

8.

Describe reasons why there are dose limitations.

Calculate adult and pediatric patient dosages for most nuclear mdicine studies.

State the relative advantages/disadvantages of dose limitations,

Compare and contrast dosing requirements for planar and SPECT imaging.

Describe dosing limitations for pregnant and breast-feeding patients.

Describe factors that affect image acquisition.

List current dosing regimens for diagnostic nuclear medicine,

Understand pediatric dosage estimates/calculations,

1

COURSE OUTLINE

1. INTRODUCTION

II, TRENDS IN RADIONUCLIDE IMAGING

III. REVIEW OF RADIATION BIOLOGY

A.B.c.

Stochastic vs Non-Stochastic EffectsRadiation Effects on the FetusDose Limitations

IV. IMAGE FORMATION AND LESIONDETECTABILITY

A. Image ResolutionB. Object ContrastC. Count Density

v. DETERMINATION OF ACTIVITY TO BEADMINISTERED

A.

B.

c’.

D,

Imaging Agent/Radionuclide

1. Photon Yield2. Photon Energy

Minimum and Maximum Activity

1. Threshold2. Absorbed Dose3. Toxic Effects

Planar vs. Single Photon EmissionComputed Tomography (SPECT)

Patient Characteristics and DosingRegimens

1. Adult

a. Women of Child-bearing Age

b. Pregnant Patientsc. Breast-feeding

Patients

2. Pdiatric

VI. SUMMARY AND CONCLUSIONS

FACTORS TO CONSIDER WHENSELECTING RADIOPHARMACEUTICAL

DOSAGES FOR DIAGNOSTIC PROCEDURES

By

Susan J. Ballinger, M. S., R.Ph., CNMT, BCNPSyncor International Corporation

Albuquerque, New Mexico

INTRODUCTION

One of the objectives of Nuclear Medicine is toprovide accurate and useful diagnostic informationregarding a patient’s condition, while keeping theradiation absorbed dose as low as reasonablyachievable. This is primarily accomplished bylimiting the amount of radioactivity administered, butnot to such an extent that the resulting image/databecomes ditiicult to interpret due to inadequate orsuboptimal information @hoton density). Patientexposure can also be reduced by using short-lived,photon-emitting (non-particulate) radionuclides thatare quickly eliminated from the body, i.e., shorteffective half-life. Usually, larger amounts of theseradionuclides can be administered compared toradionuclides with long effective half-lives, thusallowing more photons available for improvedinformation density per unit time. This phenomenonenhances image quality while shortening theacquisition time. Other characteristics of aradiotracer that may affect image outcome and patientexposure include 1) the relative abundance of photonsemitted, 2) the type of emission, i.e., particulate ornon-particulate, and 3) the photon energy. Whenlimited radiopharmaceuticals are available to image aspecific organ, it is sometimes necessary to use aradiotracer-with suboptimal physical and biologicalcharacteristics because the benefits of a correctdiagnosis, in most cases, outweigh any minimal risksto the patient (1). In this lesson, past and currenttrends in nuclear medicine dosing will be reviewed,factors affecting dose limitations will be presented,and current dosing regimens for diagnosticradiopharmaceuticals will be discussed.

TRENDS IN RAD1ONUCLIDE IMAGING

The concept of Nuclear Mdicine was firstapplied in the 1940s, when scientists attempted toquantitate the percentage of ‘3’1 taken up by thethyroid gland. Utilizing the Geiger Muller (GM)tube, the efficiency of detecting 1311gamma rays wasonly 1%, with marginal results. In the late 1940s,

2

●

●

●

photomultiplier tubes were discovered to detectindividual scintillations, and with amplification, largeelectronic pulses could be produced for eachscintillation. When coupled to a gamma ray detector,calcium tungstate, the first trials using 1311produceda detector efficiency of 25.8%, a big improvementfrom the GM tubes. The first clinical applicationinvolved an intravenous dose of 200 ~Ci of 1~11,withthe complete mapping of the thyroid gland in one andone half hours. This time-consuming, tediousprocess led scientists to attempt to improve thesensitivity of this detection system and to also makeefforts toward automating the method.

These improvements resulted in a detection systemsensitivity so high that a 24-hour thyroid uptake couldhe measured with as little as 1 uCi of ‘311.When Dr.Edith Quimhy, a member of the Human UsageCommittee of the Atomic Energy Commission, wasmade aware of this development, she stated that shewould recommend this procedure be permitted onhospital patients if the administered dose could beless than 40 uCi. This led to the production of thefirst scintillation area scanner in 1950.

When hermetically-sealed thallium-activatedsodium iodide [NaI (Tl)] in the form of clear singlecrystals became commercially available, they quicklyreplaced the calcium tungstate usd in commercialscanners. This was followed by the development offocused multichannel collimators that resulted inhigher sensitivity, allowing a smaller administereddose, a shorter scanning time, and improved imagequality. New imaging agents were developed in the1950-1960s that allowed for scanning of organsystems other than the thyroid. Examples of theseearly radiopharmaceuticals include 1311labeled humanserum albumin for brain tumor scanning, colloidal‘“8goldfor liver imaging, and 1311labeled rose bengalfor imaging the hepatobiliary tract.

Further advancements occurred with thedevelopment of a rate-controlled background cutoffsystem and photoscarming, in which images wereprinted on standard-size X-ray film, which appealedto radiologists. Again, additional radiotracersbecame available; 51Crlabeled sensitized red cells forspleen imaging, 1311labeled iodohippurate sodium forkidney function tests, and blood pool imaging agents,among others. Each of the radioisotopes described ischaracterized hy relatively high energy photons.Therefore, the rectiline~r scanner, with its thickcrystal and special collimator provided an excellentimaging device (3).

In 1957, Anger described a single crystal camera(scintillation camera) that viewed all parts of theradiation field continuously, rather than scanningfrom point to point as was necessary with the

rectilinear scanner (3,5). The collection of gammaphotons was markedly improved by use of a parallel-hole collimator. This enabled larger fields of view,shorter imaging times, sharper images, and thepossibility of time-sequencd dynamic imaging. Thisimaging system was not readily accepted in thenuclear medicine community because of the poordetection efficiency of the system when imaging with1311 It was not until‘mTechnetium by Harper etrange of ‘ymTc-labeleddeveloped in the late 1960s,camera was routine] y used.labeled radiopharmaceuticals

the introduction ofal. (3,7) and the wideradiopharmaceuti cals

which this scintillationExamples of *Tc-

developed were ‘Tc-pentetate (DTPA) and ‘mTc-glucoheptonate for brain

‘“Tc-MAA for pulmonaryand renal imaging,perfusion studies, ‘mTc-labeled polyphosphates anddiphosphonates for bone imaging, ‘mTc-sulfur colloidfor liver/spleen imaging, and various ‘Tc-labeledhepatobiliary tract imaging agents (3).

Today, commercially-available scintillationcameras employ a single sodium iodide crystalmeasuring between 11 and 20 inches (25-50 cm) indiameter and from 0.25 to 0.5 inch (0.64-1.27 cm) inthickness as the detector unit. The crystal is viewedby many photomultiplier tubes (19 to 91 or more)usually arranged in a hexagongal array (5).

The development of x-ray computed tomography(CT) in the early 1970s was a stepping stone for theapplication of the principles of image reconstructionin nuclear medicine. One of the problems withconventional radionuclide imaging is that the imagesare two-dimensional projections of three-dimensionalsource distributions. Images of structures at onedepth in the patient can be obscured by overlying andunderlying structures. An alternative approach istomographic imaging where two-dimensionalrepresentations of structures at a cer~din depth orplane are viewed in a three dimensional object (8).After the development of CT, tremendous strideswere made with emission computed tomography(ECT). The availability of small dedicated computerswith high capacity for acquisition of data made thisadvancement possible (6).

Currently there are two types of ECT utilized innuclear medicine, and they are basal on the type ofradionuclides used: 1) single photon emissioncomputed tomography (SPECT), which uses gamma-emitting radionuclides such as ‘mTc, lmI, b7Ga, and“’In, and 2) positron emission tomography (PET),which uses positron (B+)-emitting radionuclides, suchas llC, 13N, 150, 18F, bEGa,and ‘aRb, among others(10).

These two imaging modalities have an improvedsensitivity over conventional radionuclide imaging

3

TABLE 1. COMMON RADIOPHARMACEUTICAH IN CLINICAL USE

TRACER APPLICATIONS

*Tc-exametazine-c-bicisate‘1lIn-pentetate-c-medronate-c-oxidronate~c-pertechnetate

‘xl-sodium iodide1311-sodium iodide

‘Tc-rd blood cells‘Tc-human serum albumin*Tc-rnacroaggregated albumin133Xe-gas8’mKr-gas-c-pentetate-c-mertiatide‘Tc-gluceptate‘Tc-succimerlxI-iothalamate1311-iodohippurate

*’Tc-sulfur colloid~c-albumin colloid*Tc-disofenin‘Tc-lidofenin‘Tc-sestarnibi~c-teboroxime~c-tetrofosmin‘lT1-thallous chloride~c-pyrophosphate11lIn-oxyquinoline‘7Ga-gallium citrate

37Co-cymocobalamin32P-sodium phosphate

32P-chromic phosphate

‘xI-human serum albumin“ Cr-sodium chromate

‘J’I-iodomethyl-norcholesterollqlI-me~iodobeMyl-gumidlne

‘g$r-strontium chloride11lIn-satumomab pendetide1*lIn-pentetreoti(Ie

imaging of CNSimaging of CNSimaging of CSF kineticsbone imagingbone imagingimaging of thyroid, salivary glands, ectopic mucosa, parathyroid glands;

dacryocystography, cystographythyroid imaging, uptakethyroid uptake, therapyimaging of GI bleeds, cardiac chambersimaging of cardiac chamberslung perfusion imaginglung ventilation imaginglung ventilation imagingradioaerosol ventilation imaging; renal imaging and function studiesrenal imaging and function studiesrenal imagingrenal imaging

measurement of glomerular filtrationrenal imaging and function studiesimaging of RES (liver/spl=n), gastric emptying, GI bleedsimaging of RES (liver/spleen)hepatobiliary imaginghepatobiliary imagingmyocardial perfusion imagingmyocardial perfusion imagingmyocardial perfusion imagingmyocardial perfusion imaging; parathyroid imagingavid infarct imagingfor labeling leukocytes and plateletsimaging of inflammatory processw and soft tissue tumorsSchilling &sttherapy of polycythemia vera, palliative treatment of bone pain in patients with skeletalmetastasistherapy of intracavitary malignanciesplasma volume determinationsfor lab~ling RBC’Sadrenal imagingimaging of phmchromocytomas and neuroblastomas

palliative treatment of bone pain in patients with skeletal metastasiscolorectal and ovarian tumor imagingsornatostatin receptor imaging

Positron Emission TomographyAgents

‘2Rb myocardial perfusion

11C-acetate metabolism

1lC-palmitate fatty acid metabolism

13N-NH3 perfusion

150-H~0 perfusion

‘fo-co, perfusion

“c-co blood volume

18F-dwxyglucose metabolism

4

because the entire organ is imaged instead of just thesurface of the organ. More counts are needed toenable evaluation of the entire organ; therefore, the

o

administered activity may be slightly higher than fora planar study (10), The end product is improvedclinical results, and in most cases, the benefitsoutweigh the risks associated with the increasedactivity administered (6).

The continued introduction of newradiopharmaceuticals (Table 1) that have moredesirable physical and biological characteristics, aswell as improvements in camera systems, have been,and are, essential for the evolution of nuclearmdicine (3). The overall goal should be to reducea patient’s radiation exposure to as low as reasonablyachievable (ALARA) while simultaneously obtainingaccurate diagnostic information about various diseaseprocesses (l).

REVIEW OF RADIATION BIOLOGY

Stochastic and Nonstochastic EffectsLiving tissue, when exposed to radiation, can

undergo detrimental changes. These changes are aresult of physical and chemical reactions in the cellsdue to absorbed radiation energy. There is a dosethreshold point above which acute radiation injuries

mare produced and this threshold varies with the typeof tissue involved. Examples of acute radiationinjuries include extensive cellular death, total orpartial loss of organ function (e.g., bone marrowdepression), and subsequent tissue changes such asdecreased blood supply and fibrosis. These effectsare referred to as non-stochastic and they are not seenin properly conducted diagnostic nuclear medicineprocedures. This is because the absorbed doses fromdiagnostic nuclear mdicine procedures are wellbelow the dose threshold points at which the non-stochastic effects occur. Absorbed doses below thesethreshold points, however, may eventually result inan increased risk of cancer or inherited disorders.These effects are known as stochastic. As absorbeddoses exced the threshold points for non-stochasticeffects, there is an increase in severity of radiationinjury to tissue. This does not apply towardstochastic effects because there is no recognizedabsorbed dose threshold; therefore, even small dosescould possibly cause cancer induction (11).

Whenever a nuclear medicine or radiologyexamination is performed, it is assumed that everyincrement of absorbed dose to an individual may

● carry some risk, no matter how small it may actuallybe. It is difficult to establish a numerical relationshipbetween amount of exposure and frequency of effect.One reason is because the late effects associated with

low absorbed doses are not caused exclusively byionizing radiation; another reason is that these effectsmay not occur for many years after irradiation.However, risk coefficients have been developed byextrapolation from data involving larger absorbeddoses than that used in nuclear medicine and theyvary according to the dose-response relationship inthe extrapolation process. The cancer mortality riskestimates published by the International Commissionon Radiologic Protection are given in Table 2 (11).

TABLE 2: CANCER MORTALITY RISKESTIMATES BY SITE

Site of Cancer Mortality Risk(lo’sV-’)

Red bone marrow 2.0Lung 2.0Breast 2.5Bone surfaces 0.5Thyroid 0.5Total of all other tissues 5.0

Note: Data is averaged for sex ad age, therefore, theaverage risk estimate for the female br~t istwice the given value, and zero for the male.

ICRP Report 52, 19S7; p.4, with permission(11).

Radiation Effects on the FetusConsideration must also be given to the possible

effects of radiation on the developing embryo orfetus. The nature and frequency of developmentaleffects depend on the stage of development at whichexposure occurs, on the absorbed dose received, andon the type of radiation involved, Radiation-inducedcancers are also a possibility in this faction of thepopulation and could be expr~ssed during childhoodor later in adult life.

Radiation exposure during the month following thefirst day of the last menstrual period can result in anincrease in the probabilityy of spontanmus abortion.Since organogenesis is unlikely during this stage ofdevelopment, the induction of malformation in theembryo will probably not occur. In the following 2-8weeks after fertilization, when organogenesisproceeds, there is an assumed increase inradiosensitivity. This is based on malformationsobserved in exposed experimental animals atcorresponding stages of development. However,such malformations have not been observed inhumanpopulation, most likely due to the slower rate ofdevelopment of organs in humans. Developinghuman organs are apparent]y less susceptible toinduction by a brief exposure to radiation because of

5

the smaller proportion oftime (11). On the basisUNSCEAR (1986) (12),

cells dividing at any oneof experimental studies,assessed the risk of an

absolute increase of malformed fetuses to he on theorder of 5 x 10-1Gy-l (11).

During the period of 8-15 weeks after fertilization,the human forebrain is developing extensively.Studies of Japanese atom bomb survivors revealed anexcess of severe mental impairment in children whoreceived a brief radiation exposure in utero duringthis period. It may be concluded that the risk ofsevere mental retardation is a function of theabsorbed dose with an estimated risk coefficient of 4x 10-1Gy”l (11).

Dose LimitationsKnowing the associated risks of radiation to adult

and fetal populations, the ICRP introduced a systemof dose limitations (ICRP, 1977) (13). The mainfeatures are as follows (11):

1.

2.

3.

No practice shall be adopted unless itsintroduction produces a positive net benefit.

All exposures shall be kept ALARA,economic and social factors being taken intoaccount.

The dose equivalent to individuals shall notexceed the 1imits recommended for theappropriate circumstances by theCommission.

The first component refers to justification whichimplies that more accurate diagnosis or healthimprovement due to a procedure should outweigh therisk of any eventual stochastic or non-stochasticeffects induced by radiation. In other words, by notperforming the procedures there is a higher risk tothe patient’s health than the expected radiation-relatedrisk. The decision of the nuclear medicine physicianand referring physician that the procedure will be anet benefit for a patient constitutes justification forthe patient’s exposure.

A request for the in-vivo nuclear medicineprocedure should first take in to account theavailability, relative efficacy and associated risk ofalternative methods. These alternative diagnosticmodalities include radiography, x-ray computedtomography, ultrasound, and magnetic resonanceimaging (MRI).

The second and third components refer tooptimization which means that the effective doseequivalent (a measure of individual organ exposurewhen radiopharmaceuticals are received by the

patient) should not exceed that required to provide thenecessary clinical information. This can be achievedby limiting the administered activity to the smallestamount possible without interfering with the outcomeof the diagnostic procedure. The Commission has

orecommended limits of dose equivalents for individualsundergoing certain procedures in nuclear medicine(13).

The optimum activity of a radiopharmaceutical fora given diagnostic procedure can be a complex matterand is difficult to determine, especially when appliedto individual patienw. Activities needed forprocedures that produce quantitative numerical results,i.e., renal clearance, can be assessed with relative easeand precision. On the other hdnd, activities neededfor both dynamic and static imaging procedures aremore difficult to determine as one strives to optimize‘sensitivi~ and specificity of the study, The amount ofactivity needed for a nuclear medicine study dependsupon many factors. These factors include detectorcapabilities, radiopharm-aceutical characteristics, andindividual patient parameters (11).

IMAGE FORMATION AND LESIONDETECTABILITY

Lesion detection is the most important attribute ofany image in a clinical setting. The three main factorsfor lesion detection of an imaging system are image ●resolution, object contrast, and count density (orinformation density). These three factors, incombination, allow for optimal image acquisition (14).

Image RwolutionThe most important type of resolution is spatial or

geometric resolution (14). This varies primarily as afunction of the physical characteristics of the imagingdevice (15). The device is responsible for producingimages that clearly separate line sources of activityspaced at various distances or to define different-sizedregions of abnormality (4). In other words, theimaging device defines the smallest object that appearsas a distinct structure. The limiting factor for agamma camera imaging system is the collimatorresolution. Resolution can be optimized by propercollimator choice and through carefully performedquality control procedures. Even optimal Spatialresolution of about 5-10 mm in a nuclear medicinescintiscan compares poorly with the resolutionattainable from other imaging modalities. The imagesharpness for a radiograph is clearer because theresolution is only a fraction of a millimeter (14).Moreover, patient motion and artifacfi can adversely

oaffect image resolution (4).

6

Objwt ContrastObject contrast is the difference between

background activity of an image and lesion activity

●(4, 14). In a nuclear medicine scan, this refers totracer localization in an abnormality compared totracer localization in normal adjacent tissue. Objectcontrast is enhanced by selecting the most appropriateradiopharmaceutical and by imaging at the time whenthe count rate and signal-to-background activity ratioare optimal. Tomographic imaging has improvednuclear image contrast because of the various depthsthis process can detect, thus allowing isolation of theobject of interest from overlying tissue. Nuclearmedicine scintiscans have high image contrastcompared to other imaging modalities, with target tobackground ratios as high as 10 times greater (14).

Count DensityCount density is the number of counts recorded

per unit area of the radioactive source being imaged(counts/cm’) (4, 15). A minimum number of countsis needed for a difference to be observed betweenstatistical variation and abnormal accumulation ofcounts in relation to surrounding background (15).All x-ray and radionuclide images result fromcollecting large numbers of photons. There is aninverse relationship between the square root of the

●number of photons collected and the degree ofstatistical uncertainty. Therefore, higher-countdensity images allow better delineation of edges inthe image, less uncertainty, and better detection oflesions (Figure 1).

The imtiges of the he:irt were recorded to a computer using

‘nTc-labeled rcd blood cells. The images contain 10,000 counts

●(upper IcR), S0,000 counts (upper right), 500,000 counts (lowerleft), and 1,000,000 counts (lower right). The images have beennormalizwi to a similar image intensity for the purpose ofcomparison.Palmer, ct Il., 1992; p.57, with permission (14).

For most applications, the acceptable range ofcount density is between 400 and 1200 counts/cm2,with the upper end of this range being the mostoptimal for image formation. Count densities higherthan 1200 counts/cm2 add little to image quality. Ifmore photons need to be collected for an optimalcount density, the physician can either give a largertracer dose or image for a longer time. The problemwith increasing the patient’s dose is the increase inexposure the patient will receive. Administered dosesare aimed at delivering a radiation burden of less than5 rads (50 mGy) to the Parget organ. With this inmind, an increase in imaging time would be moredesirable than an increase in exposure, Thedownside to increasing imaging time is the possibilityof patient motion resulting in a degradation of theimage (14).

An adequate combination of all three of theparameters (spatial resolution, object contrast, andcount density) are required for lesion detectability(4, 15). A high resolution with poor contrmt willproduce an image that is poor quality and of littlevalue. An example of this is a lesion in the middleof a large organ where the contrast between the twois extremely low. This lesion most probably will notbe detected because it can not be distinguished fromthe surrounding organ. If this same lesion is placedin a small organ with satisfactory object contrast, itwill most likely be detected. Another example: If animaging system has good spatial resolution andfavorable object contrast between the lesion and thesurrounding tissue, a low count density could bedetrimental to the resulting image. Too low anumber of counts causes the lesion to beindistinguishable from counts caused by the statisticalnature of the random decay process (4).

DETERMINATION OF ACTIVITY TO BEADMINISTERED

There are many other fidctors that influence imageformation (Table 3) (15). Among them are 1)characteristics of the imaging agent and 2) theadministered activity.

Imaging Agent/RadionuclideIdeal imaging agents will have properties that

cause them to localize in various organs of interest.If an agent localizes in a region of abnormality, a“hot lesion” (increased photon density) is created and,if it localizes in an abnormality to a lesser degreethan surrounding normal tissue, a “cold lesion” iscreated. Whether “hot” or “cold” lesions, both aredifficult to identify if there is poor object contrast dueto low target-to-background ratios. Thus, it is

7

important to have a favorable object contrast whendistinquishing between these two types of lesionscompared to surrounding normal tissue (9).

TABLE 3: FACTORS INVOLVED IN IMAGEFORMATION

1. Characteristics of the imaging agent2. Administered activity3. Collimator design4. Detector characteristics5. Pre-image electronic processing t~hniques6. Display and rwording medium7. Image data manipulation techniques8. Patient motion

9. Artifdcts

From Rollo, 1977; p.397, with permission (15).

The type of emission of a radionuclide is alsoimportant in nuclear medicine imaging. Particulateemissions, i.e., beta or alpha particles, release a lotof energy per unit length of the path they travel.This energy is imparted to living tissue causingincreased radiation exposure to the patient. Non-particulate emissions, i.e., photons such as gammarays or x-rays, travel at a fast speed and impart lessenergy along the traveled path, resulting in less tissueinteraction. Ideally, it is best to have a radionuclidewith a high photon/particle ratio.

Two characteristics that are important involvingthe radionuclide used to label an agent are photonyield and photon energy (4, 15).

Photon Yield. Photon yield is the number ofphotons produced per disintegration of a radionuclide.High yields of clinically-useful photons are generallydesirable because the time to acquire a statisticallysufficient count density is decreased (4,15). Manyradionuclides rtilease more than one photon perdisintegration, including ‘Tc; however, not all ofthe photons released are useful for imaging. Theradiation dose to the patient can be increased if thereis a high yield of photons with too low an energy(due to tissue absorption). On the other hand, a highyield of photons with high energies can cause poorsystem spatial resolution due to an increase in scatterand septal penetration of the collimator (15).

Photon Energy. The photon energy can affect thethree parameters previously mentioned, i.e., spatialresolution, object contrast, and count density. Photonenergies in the 110 to 160 keV energy range are idealfor scintillation cameras because they are readilyabsorbed by the sodium iodide crystal and alsoreadily transmitted through body tissues. Their high

detection efficiency and high efficiency oftransmitted through the body result in highdensities. Because the photons in this energy

beingcountrange

interact with the crystal so well, more electrons canbe generated in the photomultiplier tubes, and more ●information can be gathered, resulting in a goodspatial resolution. A good object contrast can beattained when using radionuclides with photonemissions in this energy range. The high countdensity produces a differential in counts between theorgan and the lesion within the organ. Lower photonenergies have an increase in attenuation and,therefore, a decrease in this differential. Photonenergies greater than 160 KeV have improved objectcontrast, but less photons are absorbed by the crys~al,resulting in poor count densities (4).

Ideally, the radionuclide used to label the imagingagent should have a high photon yield to provide ahigh count rate. It should also have a sufficientlyhigh photon energy to allow the photons to leave theorgan being imaged, but low enough to besufficiently absorbed by the thickness of the sodiumiodide crystal being employed (4, 15).

Minimum and Maximum ActivityThe administered activity of a

radiopharmaceutical, as discussed earlier, is alsoimportant. For a given nuclear medicine procedure,the diagnostic information obtained will vary with the oamount of administered activity (11).

Threshold. There is an activity threshold pointbelow which no useful diagnostic information can beexpected (Figure 2). Above this threshold level, thediagnostic value will go up dramatically withincreasing administered activity. When an acceptablequality of the image has been reached, furtherincreases of the administered activity will notsignificant y improve the results. For eachprocedure, assessment of optimum activity should beperformed. Very little systematic exploration hasbeen done in this area (1 1).

~~ .Admlnlsterad activity

Schematic representation of the value of diagnostic informationas a functiori of amount of administered ac~ivity. From lCRP

Publication 52, 1987; p.7, with permission (11).

8

Additional factors that may limit the amount ofactivity used are the absorbed dose delivered to thepatient and the toxic effects of the

●radiopharrnaceutical.

Absorbed dose. The absorbed dose varies withthe physical characteristics of the radionuclide and thebiological characteristics of the radiopharmaceutical.For example, radionuclides like 1311deliver a highradiation dose per microcurie of administered dosage,primarily due to the large beta particle component.Conversely, radionuclides such as ‘Tc and l“I havelower associated absorbed doses because they arepure gamma photon emitters (15). In general,radionuclides that have relatively short half-lives anddo not have a beta particle component provide thelowest absorbed doses (1,4, 15).

The chemical form of the radiopharmaceuticalaffects the biologic activity. This includes where andhow long the agent will remain in the body. Ideally,the agent should only localize within the region ofinterest, and all otier activity should be eliminatedrapidly from the body (4).

Toxic Effects. Toxic effects directly related to the

administered dosage are rare. The amount of

imaging agent administered in a given study is of the

order of milligrams or less, which is a very small

amount (15). In fact, it is not generally enough to

●produce a pharmacologic or toxicologic response.

For example, a typical 10 uCi diagnostic dosage of

sodium iodide ’311 will contain only 8 x 1011 g of

iodine. This is only .00005% of the daily dietary

intake of iodine. This obviously poses no threat tothose who are allergic to iodine (l).

Therefore, the factor that most significantly affectsthe amount of activity used in a nuclear medicineprocedure is the radiation absorbed dose delivered tothe patient. In most cases, the toxic effects arerarely, if ever, a concern (15).

The administration of activity levels larger thanthe optimum amount should be discouraged. Thereare areas in the world where there are limitedresources, and the amount of activity is increased inorder to cut down on examination time. Thisincreases the productivity of the medical staff andavailability of the services. This practice should onlytake place if it is justified by the benefits.

The administration of activity levels belowthe optimum will usually lead to poor qualityimages and, possibly, errors in the diagnosis. Inmost cases, there is a small reduction in risk,

●accompanied by a large reduction in benefit.This practice should also be discouraged (11).

Planar vs. $~t ImagingThe amount of activity administered for a given

nuclear medicine scan can have an effect on themethod of data acquisition, be it traditional planarviews or SPECT. Likewise, the method of dataacquisition utilized can affect the amount of activityrequired for administration.

A planar image requires a minimum number ofcounts to achieve a reasonable image contrast. Theoptimum count density is about 1000 counts/cm2.The count density depends on the amount of activityadministered, its uptake in the organ of interest, andthe length of time the organ is imaged. In somecases, the examination time may have to beprolonged if a suboptimal amount of imaging agent isadministered. Planar imaging usually involvesimaging at different projections such as anterior,posterior, lateral and oblique. These views cancollectively give some information about the depth ofa structure, but a more precise assessment of thedepth of a structure in an object can be obtainedusing tomographic scanners (10).

Improved clinical results are achieved withSPECT because there is an elimination ofunnecessary information, both background andforeground, improving the target to non-target ratio,and resulting in a more direct image (6). Mostcameras used for tomographic imaging contain one tothree detector heads mounted on a gantry to allowrotation around the patient for 18(3oto 3~ angularsampling. The camera systems usually have an on-line computer and display system which allows theuser to choose the appropriate display grid andreconstruction filter. The term “noise” means anytype of unwanted signal in the data. Thereconstruction process used on the raw datapropagates some statistical noise, thus requiring thata larger number of counts be acquired for SPECTimages. For example, a planar image of high qualityrequires about 500,000 counts per image, whereas,an image of similar statistical quality with SPECTrequires acquisition of a much larger number ofcounts, on the order of 5-15 million counts (6,8,10).

Image noise, in most cases, is analyzed in termsof signal-to-noise ratio (S/N). The significance of thenoise depends on its magnitude compared to that ofthe signal of interest. When comparing the amountof noise generated in a planar image vs. atomographic image, one must analyze the squarepicture elements (or pixels) that form the image.Each pixel can be characterized by a total number ofcounts, NP. With standard planar images, the datafor individual pixels are independent of other pixelsin the image, so the noise in a given pixel is equal tothe square root of the pixel counts, ~‘ This

9

relationship does not apply to tomographic images,because the reconstructed value for each pixel isinfluenced by the values in other pixels crossed bythe same sampling lines. Therefore, the signal-to-noise ratio for a reconstructed image over a uniformactivity distribution is given by the followingequation:

where D is the diameter of the object or bodysection, d is the linear sampling distance, and N isthe total number of counts in the reconstructedimage. Noise is expressed in the above relationshipas a standard deviation of recorded signal counts. Astotal counts increase, the S/N will increase.However, as the number of resolution elements (D/d)increases, the S/N will decrease (8).

The fact that a large number of counts ned to beacquired in a reasonable imaging time perioddemands that the detector system be designed forhigh photon collection efficiency. One way to designthe system is to use multiple detectors around thepatient to collect several projections at once.However, even with three detector headssimultaneous y acquiring data, many collectionintervals are required which increases imaging time.This feature makes gamma camera SPECT less usefulfor dynamic imaging processes that occur withinperiods of minutes (8). Otherwise, total counts maybe increased either by counting for a longer period oftime or by administering more activity (10).

Patient Characteristics and Dosing RegimensIdeally, all nuclear medicine examimtions should

‘be individually planned in relation to the clinicalproblem. Since each patient has differentcharacteristics, i.e., age, size, and gender, the amountof activity utilized in a particular study may vary (11).

AduZt Patients. There is no universally-acceptedschedule of activity that should be administered toadult pdtients (see Table 4). With “state of the art”equipment and use of radiopharmaceuticals which arepure gamma emitters, one should use the amount thatwill ensure that the examination provides theinformation which it set out to achieve (16).

The possibility of pregnancy should always betaken into account in women of chtietig age. Inlight of this information, justification for the use ofradiopharmaceuticals must be considered beforeadministration (11),

The absorbed dose received from a diagnosticnuclear medicine study is well below that known tocause adverse effects in humans. However, it is

preferable to limit fetal exposure as much as possible(14).

ICRP (11) recommends measures and precautionsto ensure the prevention or minimization of exposureto an embryo or fetus, include the following:

There are

patient must be thoroughlyinterviewed to assess the likelihoodof pregnancy,

in some cases of question, apregnancy test may be indicated, and

advisory notices should be postal atseveral places within the nuclearmedicine department to ensuremaximum publicity and lessunintentional fetal exposure.

no currently-usd nuclear medicinediagnostic tests in which tissue radionuclideconcentrations have sufficiently long effective half-lives to expose an embryo significantly. Therefore,following the administration of a diagnosticradiopharmaceutical, there is no medical reason towait in attempting to get pregnant, as the risk to theembryo would be negligible (11).

Most radiopharmaceuticals administered topregwnt putietis deliver some radiation to the fetuseither from accumulation in adjacent organs or fromexcretion in the mother’s bladder or colon (14).Some undergo placental transfer and distribute in thefetal tissues themselves, i.e., ‘~11as iodide or ‘mTc aspertechnetate in the fetal thyroid (11).

The first consideration is to determine if the scanis necessary. Great care must he taken to be certainthat the examination is indicated. Therefore, aconsultation with the referring physician is warranted.If it is determined that the risk of not making anecessary diagnosis is greater than that of irradiatingthe fetus, the examination should be performed (11),The danger from maternal illness or death is muchgreater to the fetus than the theoretical harm ofradiation. For example, before performing aventilation/perfusion lung scan, an estimation of thefetal dose should be considered. The traceraccumulation in the bladder of the mother, with someinternal scatter from the lungs would be a largeportion of the fetus’ exposure. To minimize thisexposure, a slightly smaller tracer dose than usualcould be used, however the patient must be asked toremain still for longer imaging periods. If the chanceof lung disease is small, one might consider omittingthe ventilation part of the study. However, this partof the study contributes only a small amount ofexposure. Also, the patient should be encouraged tovoid frequently to minimize accumulation of excreted

10

TABLE 4: ADULT DOSAGES IN NUCLEAR MEDICIJNE

1 2 3

Radionharmaceutical

*Tc-DTPA(kidney)*Tc-DMSA‘“Tc-MAG,‘TcOJ-(cystogram)*Tc-MDP‘Tc-colloid(Liver/Spl een)‘mTc-colloid(marrow)‘mTc-RBC’s(denatured)*Tc-RBC’s(blood pool)

‘Tc-Alhumin(cardiac)*TcOQ-(first pass)*Tc-MAA/microsph eres‘mTcO~(ectopic gastric)*Tc-colloid(GI reflux)‘mTc-IDA(biliary)‘mTcO~(thyroid)‘mTc-HMPAO(brain)‘Tc-HMPAO(WBC)lXI-hippuran‘mI-(thyroid)lmI-MiBGl~ll-MiBG

b7Ga-citrate*TcOd-(scrotal)‘“Tc-MAA(R to L shunt)133Xe-insaline(lung per~‘Tc-sestamibi(cardi ac)‘Tc-sestamibi(tumor)‘Tc-gluconate‘lTl(cardiac)

‘lTl(tumor)

“’In(WBC)‘33Xe(ventilation)“’In-DTPA(cysternogram)‘Tc-sulfur colloid(l ymph)‘TcO:(dacryocystography)

8.03.010.02.020.03.0

29611137074740

111

20.05.010.0

740185370

5.4

2.71.9

0.6

13.52.2

8.11.121.621.613.52,24.0

1.1

4.0

2.2

200

100

70205008030040800800500801504015080

20.05.0

740

185

3.020.0

111740 20.0 740

20.03.010.01.02.52.020.020.0

7401113703792,574740740

5.010.00.38.010.0

185370

11.1296

370

1.00.2

377.5

2.0 750.6 205.4 200

.310.01,03.015.01.030.030.030.010.02.02.00.38-30

.05-.51.0.1-.2

11,13703711155537111011101110370747411.1

296-11101.875-18.5373.7-7,4

0,510.0

18.53702.2 80

30.0 1110

10.03.5

370129.5

0,510.020.0

18.5370740

1. Pediatric Task Group of EANM, 1990; p.2 (16).2. Trcves, 1995; p.fJ (27).3. Palmer, et til., 1992 (14)

11

tracer in the bladder (14).Another consideration is the scenario of a woman

who undergoes a nuclear medicine scan and thenlearns days or weeks later that she was pregnant atthe time of imaging. Nothing can be done to modifyfetal exposure at this point in time, but the questionof potential damage will arise (14). An estimate ofthe absorbed dose, and the associated risk to the fetusshould be made by a qualified expert, whenever aconcern such as this arises. Fetal irradiation from adiagnostic procedure rarely, if ever, justifiesterminating a pregnancy when basing it on relativerisk increment (11). It is important to be extremelysensitive to the concerns of the parties involved andat the same time provide unequivocal reassurance(14). According to NCRP Report No. 54 (17), dosesof less than 10 rem (O.1 Sv) are associated with asmaller risk than normal risks associated withpregnancy itself (14, 17). Altiough there is noavailable evidence to suggest that the amount ofexposure from a diagnostic nuclear medicine studycauses any harm, the nuclear medicine physicianmust strive to avoid irradiation of the fetus wheneverpossible (14).

Research has determined that the transfer ofradionuclides into the milk of breast-feeding p@”entsvaries greatly between individuals. Manyradiopharmaceuticals are secreted in breast milk, Ofthe various *Tc compounds, sodium pertechnetatereaches the highest concentrations in milk. Averagevalues for each compound were calculated and verylarge standard deviations were obtained (18).

An acceptable radiation dose to infants followingthe intake of radioactive milk is not specified. Themost recent publications recommend that the effectivedose (ED) to the baby be kept below one mSv. In astudy obtained from 60 patients, guidelines wereformulated by calculating the total thmretical activityexcreted in milk until complete decay of theradionuclide, which is higher than that measured overthe actual period of collection. Table 5 summarizesthe required interruption periods of breast-feeding(18). The following recommendations werepresented by Rubow et al. (18), and Mountford andCoakley (19). There are five categories, one ofwhich is for those radiopharmaceuticals which are notexcreted in milk to a large extent, but cause a highcontact dose to the infant. This exposure is causedby the radiation emitting from the mother when thereis close contact between her and the infant. Therecommended time period in which the mother andinfant can be near each other is referred to as theclose contact time.

1. Interruption not essential‘g~Tc-labeled disofenin, sulfurcollaid, and gluconate

11. Interruption for a definite period‘gmTc-labeled

omicrosphere,

pyrophosphate

III. Interruption with measurementOQmTc-pertechnetate, pentetate(DTPA), erythrocytesIn addition, restriction of the closecontact time to five hours over a 24hour period will reduce the effectivedose below one mSv.

IV. Cessationb7Gaand 1311

v. Restriction of close contact only (closecontact should be restricted to five hours ina 24 hour period)

‘Tc-sestamibi

In summary, breast-feeding does not need to beinterrupted after administration of *Tc-disofenin, -sulfur colloid, -gluconate, and -sestamibi. However,close contact with the infant should be restricted afteradministration of *Tc-sestamibi. *Tc-pyrophos- ●phate and *Tc-microspheres require interruptionperiods of several hours because of the release of free*Tc-pertechnetate in vivo. High activities of *Tc-pertechnetate may require interruption of breast-feeding longer than two days. For *Tc-pertechnetate, *Tc-pentetate, and ‘Tc-labeled redblood cells, interruption of breast-feeding and alsomeasurement of activity excreted in expressd milksamples is recommended. The amount of freepertechnetate that gets into breast milk variesaccording to the method of labeling red blood cells,with the in vitro method being the lowest. There isa considerabley high contact dose associated withlabeled red blood cells. Breast-feeding iscontraindicated after the administration of b7Gaand1311 b7Gahas a long effective half-life in milk (avg.of 51 hours) and this is related to its long physicalhalf-life (78 hours). The interruption periodcalculated is so long, that breast-feeding should ceasecompletely when ‘7Ga is given to a breastfeedingwoman (18),

Hedrick et al. (20) have recommended that breast-feeding should be discontinued for one and one-halfto three days following administration of lmI that ●contains lWIand ‘MIco~taminants.

It seems that less ‘Tc is excreted in milk after

12

TABLE 5: RADIOPHARMACE~ICALS JN BREAST MILK DOSIMETRY AND RECOMMENDATIONS

- Effective Dose ~ Recommendh(MBq) (ftlsv) @~) (kBq/ml)

Milk close contact

‘Tc04-*Tc04-‘“Tc-HAM‘“Tc-PYP*Tc-Disida*Tc-SC‘“Tc-DTPW‘Tc-DTPAb‘mTc-Mibi‘Tc-gluconate‘mTc-RBC’s‘7Ga-citratelqll.iodideC

100800100

15010060060090060080018540

8.2866.263.860.910.140.5016,120.480.080.280.0877.753930.40

u= Interruption period before feeding can be resumed;CU=Safe concentration at which feeding can be resumed;a =patient with very high F;b =Highest F in remaining DTPA case;c =Teff from present study;

e =~0 close contact permitted;g= Interruption period excessively long;

0.0120.940.080.470.110.120.700.701.400.701.250.970.68

3062188003260’0@738153

5.210.366.244.455.195.592.657.W3.335.51”0,0020.0010.000

IIIIIIIIIIIIIII111vI111IVIV

~= recornrnenda~ons: 1, interruption not essential; II, interruption for period u; III, interruption with measurement; IV, b-st-f~ing

contraindicated; V, limit close contact only.Adaptedfrom Rubow, et al., 1994; p, 147, with permission (18)

lung scansthan withData from

with macroaggregated albumin (MAA)human albumin microsphere (HAM).two separate sources found 0.9-11. 3%

(avg=4.3%) and 0.3-5.4% (avg=2.4%) ofadministered activity in breast milk after injections of*Tc-HAM and ‘Tc-MAA, respective] y. It appearsthat dosimetry for the two lung agents should be doneindependently and that MAA would be the agent ofchoice for lung perfusion on a breast-feeding patient.

The close contact dose after *Tc-pyrophosphateis administered to a breast-feeding patient contributeslargely to the infant’s dose. Even limiting the closecontact to periods of breast-feeding for the 24 hoursfollowing administration of the radiotracer will notreduce the total dose to below one mSv. Therefore,interruption of breast-feeding for eight hours postadministration is recommended and in this case thereis no need to restrict close contact after theadministration of *Tc-pyrophosphate. Thisadjustment will reduce the total dose to below onemSv (18). in comparison, ‘Tc-medronate has beenfound to require no interruption of breast-feeding.This may be due to the fact that the phosphonates arecleared from the blood and excreted by the kidneyssomewhat faster than pyrophosphate, thus leaving lessactivity for excretion into breast milk. Also,pyrophosphate is less stable in vivo thanphosphonates, probably resulting in more freepertechnetate available for transfer into milk(18, 19).

The general principle that nothing which couldharm the infant should be administered to a nursingmother, must be followed in nuclear medicinepractice. The preparation which would yield thelowest radiation dose to the infant and the lowestamount of activity needd to yield the necessaryinformation on a nuclear medicine image should beused (18).

Pedtin’cs. Radiopharmaceuticals utilized innuclear medicine studies are not designed for any onespecific age group. The same agents used for adultpatients are also used in children by simplymodifying the dosage of radioactivity administeredaccording to some index of body size (23). Becausethe pediatric patient has a smaller total body size andorgan mass, a child could receive many times theradiation dose (rad, Sv) of an adult if a properlyadjusted amount of radiopharmaceutical is not used(24). The biological distribution, extent of organuptake, and retention of imaging agents varyconsiderably throughout childhood and also need tobe taken into account (11,25).

The amount of a radiopharmaceutical administeredto an adult patient in a variety of procedures isreasonably standardized (Table 4), Calculations for

a pediatric dosage can be determined based upon theadult dosages given in Table 4. The pediatric dosagescaling factors are designed to ensure maintenance ofan effective concentration of the drug in the blood orother tissues (22). The amount of activity needed fora study is ultimately determined empirical] y. Thereis a wide variation in recommended pediatricdosages, indicating either disagreement on whatconstitutes an adequate examination, or lack ofattention in titrating dosages down to the least amountrequired (26).

The concept of minimal administered activity isanother concern. This relates to the minimal amountof radioactivity below which the study will beinadequate due to too low a count rate and anunacceptable imaging time. The suggested minimumradioactivity dosages in Table 6 are based onexperiences of institutions in Europe that handlenumerous neonates. The schedule of administereddosages in Table 6 are lower than those suggested incertain current pediatric nuclear medicine textbooks(16). In premature and newborn infants, theminimum radioactivity dosage should be applied(16,27). It must be kept in mind that these minimumdosages may be too low for older pediatric patients.

There are several methods available for estimatingpediatric radiopharmaceutical dosages. Examples ofsome of these methods are discussed below andsummarized in Table 7.

TABLET CHILD’S DOSE = FRACTION(F) X ADULT DOSE

RULE (F) FRACTION FORMULA

CLARK’S WIGHT (LB}150

YOUNG’S AGE (YEARS)AGE + 12

FRIED’S AGE (MO’S)

150

AREA rn,~m2(~3)

WEBSTER’S AGE + 1AGE + 7

HEIGHT HEIGHT(CHILD~174 CM

BSA BSA (CHILD)BSA (ADULT)

ml = body or organ mass of child

mz = body or organ mass of adult

BSA for Adult is 1.73 m2

14

*

●

I

TABLE 6: MINIMUM AMOUNTS OF ADMINISTERED) ACTIVITY

1 2

●Radiopharmaceutical mCi MBq mCi MBq

o

*Tc-DTPA(kidney)‘Tc-DMSA~Tc-MAG3*TcO~(cystogram)‘“Tc-MDP‘mTc-colloid(Liver/Spleen)‘Tc-colloid(marrow)*Tc-RBC’s(denatured)*Tc-RBC’s(blood pool)‘mTc-Albumin(cardiac)‘TcOd-(first pass)‘Tc-MAA/microspheres‘mTcOd-(ectopic gastric)‘mTc-colloid(GI reflux)‘Tc-IDA(biliary)‘TcO1-(th yroid)‘mTc-HMPAO@rain)‘“Tc-HMPAO(WBC)lmI-hippuranl“I-(thyroid)lnI-MiBGljlI-MiBG

‘7Ga-citrate‘mTcOq-(scrotal)‘Tc-MAA(R to L shunt)Ijjxe-in saline(lung perf)

‘Tc-sestamibi(cardiac)‘Tc-sestamihi(turnor)‘mTc-gluconate‘lTl(cardiac)‘lTl(tumor)*llIn(WBC)*TcOd-(CSF shunt)133Xe(ventilation)lllIn-DTPA(cysternogram)‘~Tc-sulfir colloid(lymph)‘TcO~(dacryocystography)‘311(metastaticsurvey)

0.60.40.40.61,10.40.60.62,22.22.20.270.60.270.60.272.71.10.270.080.95

0.27

201515204015202080808010201020101004010335

10

0.30.21.01.01.00.1

0.51.0

2.00.20.20.20.50.21.00.5

0.0251.00.10,252.00.15.02.02.01.00.150.50.050.58.01.01.00.11.0

11.17.437.037.037.03.7

18,537.0

74.07.47.4

7.4

18.5

7.4

37.0

18.5

0.92537,03.79.25

74.03.7

18574.074.037.05.5518.51.8518.529637.037.03.737.0

● 1. Pacdiatric Task Group of EANM, 1990; p.2 (16).2. Treves, 1995; p.6 (27).

15

Clark’s Rule is based on proportional bodyweights as related to the standard weight mean of 150Ibs. When radioactivity dosages are calculated byweight, the required dosage is usuallyunderestimated. One reason this occurs is that tieratios of organ to body weights in infants are greaterthan those observed in adults for the same organs(28).

Young’s Rule is basal on age and it approximatesthe body weight rule except during the first years oflife and adolescence. This rule cannot be used fornewborns and consideration must be made forvariability in growth at any given age (28).

Fried’s Rule is for pediatric patients that are lessthan one year of age. If necessary, the minimumdosage requirement may be applied with this rule(24).

The Area Rule is exponentially related to the ratioof pediatric and adult body mass or target-organmass. An accurate estimation of an imaging dosagecan be calculated by this rule because it approximatesbody or organ surface areas (28).

Webster’s Rule (modified Young’s Rule) willapproximate the Area Rule (mv3) relationship untilages eleven or twelve. For older children, Clark’sRule would be more appropriate because Webster’sRule overestimates the dosage in this age group(21,28).

The Height Rule is based on height of the childcompared to the mean adult height. It is not acommonly-usd method for pediatric dosagecalculations because of the large dosages determined,however, it maybe useful for some dynamic imagingprocedures (26).

The Bodv Surface Area Rule has been shown, byexperience, to achieve the correct dose-responserelationship with therapeutic drugs; therefore, thisrule has been adapted for diagnostic dosag~s. Bodysurface area (BSA) may be estimated from the bodyweight since it is proportional to the 0,7 power ofbody weight (Table 8) (2,23).

Estimation of dosages for pediatric patients basedon BSA generally provides a good guide for mostchildren above the age of one year, Organ growthand physiological function conform more nearly tobody surface area than to body weight, Typically,hepatic and renal function in young infants exhibitslowed metabolism and excretion compared with thatin adults. Also, the total body water andextracellular water, where many drugs distribute, arehigher in children than in adults. Dosages calculatedby weight usually lead to underdosage in children,whereas dosages calculated by BSA give highervalues, and a gredter count density. Unfortunate] y,when dosages are adjusted by BSA, the radiation

absorbed doses are slightly higher in pediatricpatients than those for adults. If dosages are adjustedby weight, the pediatric patient receives a lowerradiation absorbd dose, but much longer imagingtimes are required (2). Having the child remain stillfor the length of tie procedure can become a problemand sedation may be warra~ted (25).

TABLE 8: PERCENTAGE OF ADULT DOSEAPPI,ICABLE TO CHILDREN OFVARYING WEIGHT BASED ONSURFACE AREA.

WEIGHT SURFACE AREA MULTIPLIERKG LB (METER) FOR ADULT DOSE

3 6.6 0.20 0.126 13.2 0.32 0.19

10 22.0 0.46 0.2720 44.0 0.75 0.4430 66.0 0.99 0.5840 88.0 1.21 0.7150 110.0 1.41 0.8365 143.0 1.70 1.00

TO CALCULATE

BSA(mz) = JBODY WEIGHT(KG)1°7

11

Fmm Bell, et al., 1974; p.92, with permission (23),

Most nuclear medicine procedures involve eitherstatic imaging studies or dynamic imaging studies, ora combination of both. In the case of static images,it is possible that information density (ID) is the mostimportant consideration. It has been demonstratedthat the equivalent ID for adults can be achieved forpediatric patients if dosages are adjusted by organarea (Area Rule). Webster’s Rule closelyapproximates this dosage estimation. There is also asmall difference between dosage adjustment by organarea and by BSA, so these three methods can be usedinterchangeabley, as long as the patient is ofappropriate size for his/her age.

It has been suggested that static imaging ofchildren with an ID approximately that for an adultcan be obtained over the same imaging time ifdosages are adjusted by BSA for “thin” organs, i.e.,thyroid gland, and by weight for “thick” organs, i.e.,liver and brain (26). However, this same publicationrecommends that all s~aticimaging procedure dosagesbe adjusted by weight because of the radiation dosereceived from a BSA-derived dosage. In this case,the imaging time for “thin” organs may be longer inorder to obtain an adult ID. Bone imaging is

16

somewhat different because the tracer is distributedthroughout the extracellular fluid and if dosages areadjusted by weight, similar peak blood concentrations

●are achieved in patients of all ages. Because theentire thickness of the bone is imagd, it is alsosuggested that bone imaging is similar to imaging a“thin” organ. Therefore, dosages adjusted by eitherweight or BSA are appropriate for bone imaging.Similar considerations apply to “Gallium citrateimaging.

Dynamic imaging studies require a differentapproach, because a lot of information is needed in ashort period of time. For dynamic renal imaging,adjustments of dosages by height can providercnograms of quality similar to adult studies. Longerimaging times are not useful in this case becauserenal function is analyzed during the accumulationphase of the renogram. If a “flow” study is notincluded, less activity is needed for the analysis ofrenal function, and this applies to adults also. Thepediatric dosage estimated by height can be calculatedfrom an adult dosage of as low as 2 mCi if a flowstudy is not required.

Gated cardiac ventriculography studies can beperformed on a pediatric patient utilizing a dosageadjustment by BSA, and there should be sufficientcounts for a decent study. It is possible to

●compensate for a lower count rate by prolongingimage acquisition time or hy using fewer frames percardiac cycle to obtain the desired number of countsper frame.

In the case of first pass ventriculography,additional imaging time is not usefil in enhancingstudies performed in children. Obtaining sufficientcounts for a valid time-activity curve is veryimportant in first pass studies. Since the time-activitycurve depends on total counts rather than counts perunit area, it might appear that dosages even largerthan those calculated by height would be needed. Ithas been reported that dosages of 200 pCi/kg of‘mTc-pertechnetate can produce excellent results withfirst pass determinations of left ventricular ejectionfraction in children. This is similar to an adultdosage of 14 mCi adjusted by weight. Theyimproved results by using fewer frames per cyclewhich lowered temporal resolution. The need forunnecessarily high dosages can be prevented if thetemporal resolution is limited to no greater than thatrequired by the physiologic characteristic beingmeasured (26).

In the case of nonimaging studies, such as thyroid

● uptake, adjusting dosages by weight or BSA seemsreasonable, even though counting times will beincreased substantial yMitchell has suggested

by this approach (26).that the dosage needed for

17

thyroid uptake (or any other organ counting study)can be reduced in children by decreasing the detectordistance (22,26). In general, organ counting studiesin children can be hindered by relying on the totalradioactivity rather than information density. Thereis also an increased difficulty in limiting the field-of-view of the detector to the organ of interest in smallpatients (26).

Another consideration in pediatric dosagedeterminations is the number of particles that shouldbe administered when performing a lung perfusionstudy. Because pulmonary development isincomplete at birth, the number of particles injectedshould be limited in young patients. It is estimatedthat 10% or fewer of the eventual total number ofpulmonary capillaries are present at birth. Thecapillary number increases to 50% of the adultnumber by age three years and reaches adult numbers(nearly 300 x 10Vcapillaries) by age eight to 12 years(29). The recommended radioactive dosage of ‘mTc-MAA is 25-50 pCi/kg and the recommended particlevalues are as follows (30):

Nanates: 10,OOONewborns: 50,000One year old: 165,000Three year old: 250,000

It should be noted that the particle number should bereduced for patients with suspected or known right-to-left shunt to decrease the chance of systemicembolization from occurring. The number ofparticles should also be reduced for patients withpulmonary vascular disease, i.e., pulmonaryhypertension to eliminate any further perfusionproblems (30).

SUMMARY AND CONCLUSIONThere are many things to consider when a

radiopharmaceutical dosage is administered to apatient. If more than one radiopharmaceutical can beuse41 for a procedure, one should consider thephysical, chemical, and biological properties of each.The type of imaging system that is available in thenuclear medicine department may have a bearing onthe type or amount of radiotracer to use. SPECTimaging devices require much more datamanipulation and this can cause increased amounts ofunwanted noise. Thus a larger amount ofradioactivity may be needed with SPECT incomparison with planar imaging. Attention must begiven to the particular organ system that is beingassessed, and further consideration given to therequirements for dynamic flow studies or staticimages. Dynamic flow studies may require a largerdosage to increase the count density over the shortcounting periods. Patient characteristics are very

important in dosage determinations, For example, aptiiatric patient will require a much loweradministered activity compared to an adult patient.Finally, another related factor in dosagedeterminations is the experience of the nuclearmedicine staff, including the nuclear medicinephysician, the nuclear medicine technologist, and theradiopharmacist. If certain information is 1acking, itis the responsibilityy of each party to obtain thismissing information prior to performing the

procedure. The ultimate goal is to provide an

accurate diagnosis without compromising the care and

safety of the patient.

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QUESTIONS

1, Which of the following radiopharmaceuti-cal characteristics is not a significantconsideration in determining dosages fordiagnostic procedures?

A. radiation absorbed doseB. toxic effwts (chemical toxicity)c, effwtive half-lifeD. photon abundance

2. The first images of the thyroid gland innuclear medicine were obtained usinga(n):

A. GM tubeB. Anger camerac. Rwtilin~r scannerD. SPECT system

3. An increased risk of cancer or inheriteddisorders are possible results fromradiation exposure at low doses and arereferred to as:

A, toxic effectsB. non-stochastic effectsc. threshold effectsD. stochastic effects

4. In a female patient, the cancer mortalityrisk due to radiation exposure is highestat which site in the body?

A. lungB. breastc. rd bone marrowD. thyroid

5. Which of the following is not a factorthat can affect the development of a fetuswhen it is exposed to radiation?

A, type of radiationB. absorbed dosec. development stageD. length of nuclear

ceduremedicine pro-

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6. According to the ICRP, when the risk ofthe patient’s h~th from a disease isgreater than the radiation-related riskfrom undergoing a nuclear medicineprocedure, there is adequate forthe procedure to be performed.

A. optimizationB. dose limitationc. remunerationD. justification

7. An imaging device which producesimages that show a clear separationbetw~n distinct sources of activity isknown

A.B.c.D.

to have a good

object contrastcount densityspatial resolutionimage sharpness

8. The ability to detwt tracer localization ina lesion compared to normal adjacenttissue is termed:

A. object contrastB. count densityc. spatial resolutionD. image sharpness

9. An idd count density for a planar imagewould be:

A. 100,000 counts/cm2B. 10,000 Counts/cm*c. 1000 counts/cm2D 100 counts/cm2

10. The best combination for an adquateimage would be:

A. low count density/good spatialresolution

B. high count densitylpoor spatialresolution

c. low count density/poor spatialresolution

D. high count density/good spatialresolution

11. An idd photon energy range forimaging with an Anger camera is:

A. 50-100 KeVB. 110-160 KeVc. 200-500 KeVD. 140-250 KeV

12. The activity level below which no usefuldiagnostic information is obtained isknown as the:

A. thresholdB. saturation pointc. optimum activityD, plateau

13. Which of the following radionuclidesdelivers the highest radiation dose permicrocurie administered?

A, 99MTC

B, 131I123c. I

D. 81mKr

14. A response to the non-radioactivechemical portion of a radiopharma-ceutical (carrier) would be aeffect .

A. radiation-inducedB. diagnosticc. therapeuticD. toxicologic

15, SPECT imaging requires more activitythan planar imaging because:

A. the acquisition time is longerB, statistical noise is higherc. more detector hinds are usdD. it r~uires 500,000 counts/image

●

e

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16.

●

17.

8.

19.

20.

●

The signal-to-noise (S/N) relationship forSPECT imaging is described by which ofthe following statements?

A, as resolution elements increase,the S/N increases

B. as number of counts increases, theS/N decreases

c. as the diameter of sectionincreases, the S/N increases

D. as resolution elements increase,the S/N decreases

A woman was injected with ‘%Tc-sestamibi for a myocardial perfusionstudy and then two days later she learnedthat she was thr= w=ks pregnant. Whatshould be done?

A. The pregnancy should beterminated.

B. The study should be repeated.c. An estimate of the absorbed feti

dose should be made.D. All of the above,

The amount of radiation exposure to apregnant mother that is considered saferthan normal pregnancy risks is:

A. < 10 rem

B. 20 remc. 30 remD. 40 rem

An acceptable effective dose to an infantthat is breast-feeding would be below:

A. 1 mSvB. 2 mSvc. 5 mSvD. 10 mSv

The recommendation for a breast-feedingpatient that has been injected with 9hTc-medronate is:

A. no interruptionB. cessationc, interruption with measurementD. restrict close contact time

21. The recommended interruption time forbreast-feeding if the mother was injectedwith 9%Tc-pyrophosphate is:

A. 8 hoursB, 16 hours

c. 24 hoursD. 32 hours

22. A pediatric dosageon age is:

A. Webster’sB. Clark’sc. Young’sD. Fried’s

rule that is not based

23. A normal adult dosage for a bone scanusing ‘gmTc-medronate is 20 mCi, The@iatric dosage for a child that weighs40 lbs estimated by utilizing the BodySurface Area Rule is approximately(assuming BSA for an adult is 1.73m2):

A. 6 mCiB. 8 mCic. 10 mCiD. 12 mCi

24. Using the same information given inquestion #23, the pediatric dosagecalculated by utilizing Clark’s Rule isapproximately:

A. 5 mCiB. 7 mCic. 9 mCiD, 11 mCi

25. Which of the following is not a reason tolimit the number of particles of 9%Tc-macroaggregated albumin?

A. pulmonary hypertensionB. pulmonary embolismc. right-to-left shuntD. newborn patient

21

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