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Radionuclide imaging
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SUDARSAN AGARWALsushiagarwal@gmail.com
PINNAMANENI MEDICAL COLLEGE, VIJAYAWADA
Radionuclide Imaging & Its Applications
Atom
Atom
Electromagnetic Spectrum
Ionising radiation
• Alpha radiation – 2N+2P• Beta radiation – electron emitted by
a nucleus• Positron -similar to electron except
that it has a positive charge. PARTICULATE
• X-Rays• Gamma rays EM RADIATION
Types of Ionizing Radiation
Alpha ParticlesStopped by a sheet of paper
Beta ParticlesStopped by a layer of clothingor less than an inch of a substance (e.g. plastic)
Gamma RaysStopped by inches to feet of concreteor less than an inch of lead
RadiationSource
Gamma rays are not charged particles like a and b particles.
Gamma rays are electromagnetic radiation with high frequency.
When atoms decay by emitting a or b particles to form a new atom, the nuclei of the new atom formed may still have too much energy to be completely stable.
This excess energy is emitted as gamma rays
Accurate Diagnosis is key to Surgical practice
Accurate Diagnosis is key to Surgical practice
• X rays , CT
• Ultra Sound, MRI
• SPECT , PET
MRI SPECTfMRI
X-Ray
CTUltrasound
Diagnostic Procedure
Typical effective
dose (mSv)
Equivalent no. of chest radiographs
Approximately equivalent period of natural background
radiation
Chest X ray 0.02 1 3 days
Thyroid(Tc 99m)
1 50 6 months
Bone (Tc 99 m)
4 200 1.8 years
PET 5 250 2.3 years
CT abdomen 10 500 4.5 years
Hybrid Imaging
Hybrid Imaging
• PET-CT: radionuclide imaging devices are combined with CT in a single imaging system
• The resulting images display the functional data obtained from the radionuclide distribution (usually in color) overlaid on the anatomical information from CT (usually in grey scale)
Radiotherapy xNuclear Medicine
Nuclear medicine
• Nuclear medicine is a subspecialty within the field of radiology that uses very small amounts of radioactive material to diagnose or treat disease
• We need a short-lived radio nuclide which has to be combined to a pharmaceutical of interest and injected iv and this radio pharmaceutical goes and attaches to the organ of interest and we can catch the gamma rays emitted by it with help of gamma cameras and pictures are reconstructed in computer
• (in amounts of Pico molar concentrations thus not having any effect on the process being studied)
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
SPECT
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
Ideal Radionuclide
• Emits gamma radiation at suitable energy for detection with a gamma camera (60 - 400 kev, ideal 150 kev)
• Should not emit alpha or beta radiation
• Half life similar to length of test• Cheap• Readily available
Technetium
• This is the most common radio nuclide used in Nuclear Medicine.
• Taking its name from the Greek work technetos meaning artificial , it was the first element to be produced artificially.
99mTc
Excited Nucleus
Gamma ray
99Tc
Stable Nucleus
Photon Decay
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
Ideal radiopharmaceutical
• Cheap and readily available• Radionuclide easily incorporated
without altering biological behavior• Radiopharmaceutical easy to prepare• Localizes only in organ of interest• t1/2 of elimination from body similar to
duration of test
• Thyroid scintigraphy• Salivary gland study• Meckel’s diverticulum
scintigraphy
99mTc pertechnetate
• Interictal PET• Cerebral metabolism PET• Tumor imaging
18 FDG
• Parathyroid scintigraphy99mTc MIBI
• Bone scintigraphy
99mTc polyphos
phate
• Cardiac ventriculography• GI bleed study
99mTc red blood cells
• V/Q scan99mTc
albumin
99mTc sulphur colloid
• Esophageal transit and reflux
• GI bleed study
99mTc leucocytes
• White cell scintigraphy
99mTc iminodiacetic
acid derivatives
• Hepatobiliary study
• Diuresis renography • Renal tract obstruction
99mTc DTPA
• Static renal scintigraphy• Renal scarring
99mTc DMSA
• Somatostatin receptor study
111In pentetreo
tide
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
1. RADIONUCLIDE
2. PHARMACEUTICAL
3. GAMMA CAMERA
Gamma Camera
A gamma camera consists of three main parts:
Electronic systems
Detector
Collimator
Gamma Camera
Positron Emission Tomography
• PET is a nuclear medicine imaging technique that provides high-resolution tomographic images of the bio-distribution of a radiopharmaceutical in vivo .
• A PET scan measures important body functions, such as blood flow, oxygen use & glucose metabolism
• Radiopharmaceutical consists of positron-emitters, usually very short-lived and produced in cyclotrons.
• 18 F being one of the most optimal positron emitters for imaging
Glucose
FDG
Plasma Cell
Transport Phosphorylation Glycolysis
Glucose
18F-FDG 18F-FDG-6-P
Glucose-6-PGlycolysis
Glucose
18F-FDG
FDG
• Half-life (T 1/2 ) is 110 minutes
• Low average positron energy of 0.63 MeV
• Average positron range in tissue of 0.3 mm
• Delay a PET scan by 2 -3 weeks after surgical intervention
• 2 -3 weeks interval after chemotherapy.• 3 months after radiation therapy,• 6 to 8 weeks post-radiation therapy-
surgery.• Should not be performed on pregnant and
breast feeding patients.
• Malignant cells show an increased rate of glucose metabolism ,probably due to presence on cell surfaces of an abnormally large number of glucose transporters, along with increased hexokinase-mediated glycolysis and a reduced level of dephosphorylating by glucose -6-phosphate.
Uses • Detect primary , secondary cancer and
metastasis • Assess the effectiveness Cancer chemo therapy • Cancer recurrence • Mapping of brain and heart function • Evaluate brain abnormalities, such as tumors,
memory disorders and seizures and other central nervous system disorders
• Determine blood flow to the heart muscle and thus determine the effects of a heart attack, or myocardial infarction
Arrow points to "dead" myocardial tissue.
PET scan of a heart
Cardiac Imaging
Cerebral Imaging
• 99mTc-HMPAO : cross to BBB and fix in the brain proportionally to perfusion
• 18FDG : glucose metabolism• 99mTc-TRODAT : dopamine transporter• 111In-DTPA, 99mTc-DTPA : CSF dynamics, V-P
shunt patency study
PET image showing malignant breast mass (not revealed by CT, MRI or Mammo)
PET image of same patient with enlarged left axillary lymph nodes
The role of PET after chemotherapy
• Many neoplasms have an enhanced glucose metabolism compared to normal tissue.
• FDG provides functional data on tumor metabolism, complementary to morphologic imaging studies.
• Standard tool for decision making in lymphoma, Hodgkin`s disease, different solid tumors post chemotherapy.
• Germ cell tumors (GCT) are characterized by a high FDG uptake.
• Advantages• Disadvantages• Safety and Risk
Advantages
• Assesses body function and in monitoring flow rate
• Can measure body composition using dilution analysis.
• Whole body scanning • Response to radiotherapy and
chemotherapy
Disadvantages
• Generally poor resolution compared with other imaging modalities
• Radiation risks due to administered radionuclide
• Can be invasive, usually requiring an injection into the blood stream.
• Disposal of radio activity waste. • Relatively high costs associated with radio
tracer production and administration.
Safety and risk
• Nuclear medicine is not safe for the use of human beings, so therefore should not be used on healthy people.
• Also the procedure is not recommended for pregnant women because unborn babies have a greater sensitivity to radiation than children or adults.
Safety and risk
• Radioactive substances are emitted in to the body so the safest way is to use a radio nuclide which has a short half life, so it can decay to a safe level in the fastest possible time.
Safety and risk
• Most of the administered radioactive isotopes is excreted as urine via the kidney and bladder but same is excreted as perspiration and saliva. This means that the patient has radio active substances on their skin and should take extra care when around other people.
Safety and risk
• Safety precautions to be taken when near a patient has been injected with radioactive substance. Wear a pathology gown and disposable gloves also minimise the time spend with the patient and maximise the distance from the patient.
GIT
• Evaluates hepatocellular function and patency of the biliary system
• Performed with a variety of compounds that share the common iminodiacetate moiety
• Although it is an excellent test to decide whether the common bile and cystic ducts are patent, biliary scintigraphy does not identify gall stones or give any anatomic information
Hepato biliary Imaging
Red: A lipophilic component
Blue : A polar component
• HIDA - Little used today• DISIDA (Disofenin) -85% extracted by
the hepatocytes• BRIDA (Mebrofenin) -98% extracted
by the hepatocytes
IDA Derivatives
• The lipophilic component : binding to hepatocyte receptors for bilirubin
• Transported through the same pathways as bilirubin, except for conjugation
Pathways of IDA derivatives
Normal Study
• Immediate demonstration of Hepatic Parenchyma
• Normal Liver (5 mins),
• Intrahepatic Bile ducts (10-15 mins),
• CBD, GB & Duodenum (15-30 mins),
• Small Intestine (>30 mins)
Filling Phase
Emptying phase
Indications
• Functional assessment of the hepatobiliary system
• Integrity of the hepatobiliary tree– Evaluation of suspected acute
Cholecystitis– Evaluation of suspected chronic biliary
tract disorders– Evaluation of common bile duct
obstruction– Detection of bile extravasation– Evaluation of congenital abnormalities
Contraindications
• Hypersensitivity to– IDA derivative– Local anesthetics of the amide type
• Cardiac arrhythmias• Pregnancy
Acute Cholecystitis
• Investigation of choice is Ultrasound• Most effective investigation is Radionuclide biliary
scanning
• No filling of Gall bladder after 4 hours of injection indicates obstruction
• A normal HIDA scan excludes it. 100% negative predictive value.
Diagnostic test Sensitivity Specificity
Ultra sound 85% 95%
Tc HIDA scan 95% 95%
Biliary Atresia
Excluded by demonstrating transit of radiotracer into the bowel
Bile Leaks
• Most appropriate non-invasive imaging technique for evaluation of bile leaks
• Sensitivity: 87%, • Specificity: 100%
• Radionuclide imaging of liver and spleen depends on the function common to both i.e, phagocytosis.
• The most commonly used agent is 99m Tc Sulphur colloid.
• In normal scan there is homogenous distribution of 99m Tc Sulphur colloid through out the organ
Liver & Spleen
SMALL INFARCTING SPLEEN
99mTc COLLOID STUDY AFTER SPLEENECTOMYSHOWING VIABLE AND FUNCTONING SPLENIC TISSUE IN THE OMENTUM
LIVLIVER SECONDARIESER SECONDARIES
Tc SULPHUR COLLOID –KUPFER CELLS
Tc HIDA HEPATOCYTES
• The Meckel ’s scan is performed by giving Tc Pertechnetate , which is taken up by the ectopic gastric mucosa in the diverticulum and localized with scintigraphy
• The diagnosis of Meckel’s diverticulum is difficult.
• Plain abdominal radiographs, CT, US are rarely helpful.
Meckel’s Scan
Meckel’s in Children
• Single most accurate diagnostic test for Meckel’s is scintigraphy with Tc Pertechnetate
• Its preferentially taken up by the mucus secreting cells of gastric mucosa and ectopic gastric tissue in the diverticulum
Meckel’s in Adults
• As ectopic gastric mucosa is reduced, agents like pentagastrin, glucagon and cimetidine are used
• Pentagastrin indirectly increases the metabolism of mucus producing cells
• Glucagon inhibits peristaltic dilution and washout of intraluminal radionuclide
• Cimetidine decreases the peptic secretion and therefore retards the release of pertechnetate from the diverticular lumen, thus resulting in higher radionuclide concentrations in wall of diverticulum
NORMAL STUDY
WITHOUT H2 BLOCKADE SO TRACER IS SEEN IN THE INTESTINAL LUMEN DUE TO GASTRIC SECRETION OF THE TRACER.
MECKEL”S DIVERTICULUM IN THE RIGHT SIDE OF THE PELVIS
Normal Study
Achalasia
Achalasia
GI Bleed
• Tc labeled RBC is the most sensitive but least accurate method for localization of GI bleeding
• With this technique, the patient’s own RBC s are labeled and reinjected.
• The labeled blood is extravasated into the GI tract lumen, creating a focus that can be detected scintigraphically.
• Multiple images are collected over 24 hours
GI Bleed
• The tagged RBC scan can detect bleeding as slow as 0.1 ml/ min
• Unfortunately, spatial resolution is lacking, and blood may move retrograde in the colon or distally in the small bowel.
• If RBC scan is negative, angiography is unlikely to be revealing. Thus its used as a guide to the utility of angiography
INDICATIONS1. RECURRENT BLEEDING2. ENDOSCOPY IS
INCONCLUSIVE3. COMORBIDITIES
99mTc COLLOID99mTc RBC
Renal System
The main tracers used in evaluation of the kidney:
• DMSA : Di Mercapto Succinic Acid
• DTPA : Di-ethylene Tri-amine Penta-Acetic acid
• MAG3 : Mercapto Acetyl triGlycine
99mTc-DMSA :
• 99mTc-DMSA is cleared by both filtration and secretion, but the clearance is relatively complex and it does bind to parenchymal tissues.
• It is useful as a renal cortical imaging agent.
99mTc-DTPA:
• 99mTc-DTPA is primarily a glomerular filtration agent.
• It is also useful for evaluation of obstruction and renal function.
• It is less useful in patients with renal failure.
99m Tc-MAG3:
• 99m Tc-MAG3 is cleared by tubular secretion, and no glomerular filtration occurs.
• The tracer is well suited for evaluation of renal function and diuretic scintigraphy
• Also, it is an excellent tracer to evaluate renal plasma flow.
Procedure
• After a bolus injection of the tracer, images are obtained that can be used to estimate relative renal function.
• When the tracer reaches the collecting system, a diuretic is given and half-life is calculated based on the slope of the curve in response to the diuretic.
Renal Cortical Scintigraphy
• Done with 99mTc-DMSA
• Acute infection can produce abnormalities in the scan; and if the test is being performed to evaluate for cortical scarring, it should be done at least 3 months after an acute infection
Image of the kidneys obtained 3 hours after administration of 99mTc-DMSA shows that the left kidney is decreased in size, and contains several focal cortical defects, most notably at both poles.
Diuretic Scintigraphy:
• Diuretic scintigraphy is performed with DTPA or MAG3.
• MAG3 is more useful in patients with renal insufficiency, but DTPA is more economical.
• Diuretic scinitigraphy offers a quantitative assessment of obstruction and does not require an invasive procedure, intravenous iodinated contrast medium, or anesthesia.
Dynamic function images over 40 minutes demonstrate good uptake of tracer by both kidneys & prompt visualization of the collecting systems. A slight relative delay in clearance from the right kidney is noted.
Horse Shoe Kidney
Ectopic Kidney
Radioactive Iodine Uptake test
• Is less widely used because of more precise biochemical measurements of T3 T4 TSH
• This test in the past involved oral administration of Iodine 123
• A normal result is 15-30% uptake of the radionuclide after about 24 hours.
• Use of Iodine 123 is preferable over Iodine 131(8 days) because of a shorter half life(12 hours) and lesser radiation exposure
Thyroid - scintigraphy
99m PERTECHNETATETrapped but not organifiedCompetes with iodide for uptakeCheap and readily available
IODINE (123I or 131 I)Trapped and organifiedBetter for retrosternal goitresExpensive, cyclotron generated
NORMAL THYROID UPTAKE
COLD NODULE
HOT NODULE
• 20% of cold nodules are Malignant• 5% of hot nodules are Malignant
• Thus routine isotope scanning is no longer used to distinguish Benign from Malignant
Mechanism of ActionRadioiodine nuclide release energy beta & gamma
• I 131 ablates principally due to the short range beta radiation. It destroys cells at the end of their path
• The accompanying high energy penetrating Gamma ray radiation mostly escapes the patient producing unwanted radiation fields
Indications for Thyroid Scintigraphy
1. Thyroid nodules2. Thyrotoxicosis3. Goiter4. Ectopic thyroid5. Thyroid cancer6. Retrosternal mass7. Work up of neonates with low T4 and/or high TSH8. Occult thyroid malignancy9. Metastasis10.Swellings in thyroid region
ContraindicationsAbsolute
1. Pregnancy
2. Breastfeeding
Relative
1. Bone marrow depression
2. Pulmonary function restriction.
3. Salivary gland function restriction.
4. Presence of neurological symptoms.
Short-term complications
• Radiation thyroiditis(transient)• Sialadenitis • Gastritis 30% • Bone marrow depression• Xerostomia• Nausea/vomiting • Hypospermia
Long-term complications
• Radiation pulmonary fibrosis• Permanent bone marrow depression• Chronic hypospermia or azoospermia• Early onset of menopause• Chronic dry eye• Hypoparathyroidism (rare and
transient)
Ectopic Thyroid
Radio Iodine Ablation
GravesThyroid cancer
Radio Iodine Ablation
GravesThyroid cancer
Graves disease
• RAI has been used since 1940 (more than 50 years) for treating thyroid disease
• High rate of success with permanent cures affected and few undesirable effects for hyperthyroid & thyroid cancer
• The majority of patient receive anti thyroid drug but the success rate is limited
• Anti thyroid therapy failed, prime candidate for radioiodine therapy
Tc 99m PertechnetateThyroid scintigram
• Symmetrically enlarged gland
• Homogenous tracer distribution uniform uptake without nodularity(occasionally cold nodule seen)
• Prominent pyramidal lobe
GRAVES DISEASE
AUTONOMOUS NODULE
MNG WITH HYPERACTIVE NODULES
SOLITARY COLD NODULES
115
Treatment• 3 option :
– medical therapy antithyroid drugs– radioactive iodine– surgery thyroidectomy, partial or
complete surgical• None is the best treatment• USA radioactive is the first choice
(69%)
Percentage relapse of hyperthyroidism
Cure rate
• 59.1 % (6th month)• 72.7 % (12th month)• 92.0% (24th month)
• Return to normal T4 Take 2-6 months• During interval May need to continue
antithyroid drugs • Monitored Hypothyroidism and recurrent
hyperthyroidism • There is no optimal dose for RAI ~
controversial• Goals for RAI treatment vary from
inducing hypothyroidism to restoring euthyroidism
Before radioiodine therapy :
• Stop Antithyroid drugs 3-4 wks before
• Shall not have iodine containing injection/tablets for 4 months
• Patient have to fast overnight & an hour afterwards
Take home message (Graves)
• Iodine-131 therapy has been available for over 50 years
• There is no standard treatment for Graves’ hyperthyroidism (medical, surgical and radioactive iodine)
• RAI is Proven to be save, effective and economical form of treatment for thyroid diseases
• Appropriate patient selection & explanation the expected outcomes are essential
Radio Iodine Ablation
GravesThyroid cancer
Radio Iodine Ablation
GravesThyroid cancer
Thyroid cancer
• Incidence of thyroid cancer is increasing --Mortality rate of 2-5%
--Recurrence rate post-lobectomy 5% - 20%
• No doubt that surgery is the primary treatment
Total thyroidectomy is the choice
• Surgery alone has remained inadequate to ensure complete cure
RAI Decreased recurrence and death rates in the following ways:1.Destroyed remaining normal thyroid tissue2.Destroys occult microscopic cancer3.The use of higher doses of I-131 treatment
permits post-ablative total body scanning
RESIDUAL CA THYROID TISSUE
METASTASIS IN CERVICAL &MEDIASTINAL LN
• Follicular thyroid cancer demonstrate a capability of taking up iodine, although less than that of normal thyroid cells.
• 50% of papillary carcinomas are also able to take up iodine and the presence of follicular elements on histology is an indicator of iodine uptake capabilities.
• Medullary, anaplastic carcinomas and lymphomas of the thyroid do not take up I-131, which therefore has no role in therapy following ablation of remnant thyroid tissue.
• Medullary thyroid cancer could be treated with I-131 MIBG (metaiodobenzylguanidine)
Optimal dose
• Ablation dose : 30 – 200 mCi • Metastatic lesions : 150 – 300 mCi • Conservative approach 150 mCi• Repeated treatments were given
but not exceeding a cumulative dose of 1000 mCi
Elimination
• I 131 leaves through saliva, sweat, blood, urine, faeces
• Majority of administered RAI has been extracted after 48 hours
Near / total thyroidectomy
Thyroid / whole body scan
Positive Negative
Radio ablation80-100 mCi
Hormone substitution/suppression
• Tg• Whole body scan
Positive Negative
Radioiodine therapy100-150 mCi
4-6 week post-surgery
5 months 1 month hormone off
Survival rate :• 91% (322 patients) up to 15 yrs • 90-100% up to 7 yrs with or without local or regional metastases
Preventive ablation
Key to success in thyroid Cancer
• Early detection• Adequate thyroidectomy• Post operative radioiodine therapy• Meticulous follow-up surveillance
Take home message( Ca Thyroid)
• Radioactive Iodine recommended as an adjunctive therapy (ablation / preventive) for thyroid cancer after thyroidectomy for the complete management of well-differentiated thyroid cancer
• External beam radiotherapy for Anaplastic ca
• Radiation exposure after a latent period of 30 years can cause Papillary cancer
• RIA is best for Follicular cancer
Future Trends
• Monoclonal antibodies or their fragments are potentially ideal vehicles to carry radioisotopes to specific sites within the body
• But radiolabel has to be inserted without affecting the binding site
Thank you…
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