Medical Radionuclides

Medical Radionuclides

February 17SNAL.

Robert AvakianYerevan Physics Institute

Medical Radionuclides, Applications, Producers and Consumers

Current Production Issues

New concept advantage - introducing electron accelerators

Next steps

Agenda

Technetium 99mTc 99m is the most commonly used radionuclide (80%) Tc is the chemical symbol of technetium. 99 is its mass number. The m denotes 'metastable',

Technetium, which is not found in nature, was first discovered by Perrier and Segre in 1937 in a sample of molybdenum that had been irradiated in the Berkeley cyclotron.

It is useful for several reasons:

It can be easily combined with several pharmaceuticals.

Its half-life of six hours is long enough to allow practical imaging but not so long that the patient, public and environment are over-burdened with radiation.

It gives off gamma rays at 140keV which is a good match to the sensitivity range of the Gamma Camera.

It is a pure gamma emitter.

Technetium 99m ApplicationsApplication of radionuclides in diagnostics and medical treatment gave start to nuclear medicine.

It is used primarily to locate tumors in the body, monitor cardiac function following heart attacks, map blood flow in the brain andguide surgery.

The influence of the ionizing radiation on the biological objects led to the modern technology that allows physicians to irradiate only selected cells of tumor instead of the entire area.

The advantage of the radionuclide therapy is the absorption of radiation by pathological centers so that the sound tissues remain intact. Demand for Purity

Medical radionuclides have to have high radiochemical purity, which demands complicated radiochemical technology.

Technetium 99m Consumers

Technetium-99m became widely used in the late 1960s and early 1970s, and its use has grown dramatically ever since. It is by far the dominant radioisotope for diagnostics; demand for 99mTc is expected to grow by ~ 8-20 % per year over the long term.

80% of all nuclear medical procedures currently performed in the United States use the radioisotope Technetium-99m

More than 17 million 99mTc scans are performed annually in the United State, providing diagnostic images of almost every organ in the body. The average dose about 20 mCi. Thus, the total amount of 99mTc annually administered in the USA is 350000 CI.

Problem: Because 99mTC decays so rapidly, a substantial portion of total production quantity is lost before it can be administered.

http://images.google.am/imgres?imgurl=http://imagecache2.allposters.com/images/pic/CMSPOD/195-5177~Technetium-99-Nuclear-Med-Bone-Scan-Whole-Body-Posters.jpg&imgrefurl=https://www.allposters.co.uk/-sp/Technetium-99-Nuclear-Med-Bone-Scan-Whole-Body-Posters_i4257710_.htm&usg=___bXIEi10IdBru_fRjvvklGNCK3Q=&h=450&w=337&sz=21&hl=hy&start=9&tbnid=FeM0IhFnKdEYdM:&tbnh=127&tbnw=95&prev=/images%3Fq%3Dtechnetium%2Bscan%26gbv%3D2%26hl%3Dhy%26sa%3DG

Technetium 99m ProducersThe two main sources in the world (particularly for 99mTc which is used in 80% of scans) are:

•In Europe the High Flux Reactor in Petten the Netherlands.

•For the North America the National Research Universal Reactor in Chalk River Ontario Canada.

National Research Universal Reactor

Chalk River Ontario Canada

High Flux Reactor Petten the Netherlands

Technetium 99m Procedure

The reactors use highly enriched uranium, as fuel source and a source material from which to create 99Mo . 99Mo has a half-life of 66 hours, it progressively decays to technetium-99m.

Molybdenum-99 (99Mo) Technetium-99m (99mTc)

Technetium 99m generators are supplied to hospitals from the nuclear reactor where the isotopes are made.

lead pot enclosing a glass tube containing the radioisotope. contain molybdenum-99, with a half-life of 66 hours, which progressively decays to technetium-99m. Tc-99m is washed out of the lead pot by saline solution when it is required. After two weeks or less the generator is returned for recharging.



New concept advantages, introducing electron accelerators

Next steps

Agenda

Current Production IssuesReliabilty & Availabilty

Physicians and patients around the world are increasingly anxious about the shortage of nuclear isotopes used in medical imaging. The two main reactors are relatively old and it’s not clear how long they might last.

In 2007 in 2008 both reactors have anticipated and unanticipated shutdowns and subsequent Isotope shortage become subject of public outcry. There are no near term or even long term solutions being implemented that could provide a reliable and adequate supply for Europe and North America

National Research Universal Reactor

Chalk River Ontario Canada

High Flux Reactor Petten the Netherlands

Current Production IssuesEcology & Security

The current 99Mo production technology relies on the nuclear fission of 235 uranium

•The entire assortment of fission products is produced along with the 99Mo, therefore the quantity of radioactive by-products produced with fission product 99Mo is far more than the quantity of 99Mo obtained.

•Most of these by-products are useless, and this causes a large amount of radioactive waste to be created along with desired 99Mo product.

•Worldwide concerns about the transport of weapons-grade material (anti-terrorism)

Current Production IssuesCost effectiveness

The reactors themselves are expensive. The price of the product needs to be subsidized

The average cost of new reactor according Thomas Ruth, Nature 29Jan.2009 ia $500 Mln-$1 billion.



New concept, electron accelerators, feasibility, advantages

Next steps

Agenda

New ConceptElectron Accelerators System

New concept for the production of 99mTc and many other isotopes based on distributed electron accelerators system. The radioactive decay parent of 99mTc, 99Mo is produced from 100Mo by photoneutron reaction..

New ConceptFeasibility

Experimental research of feasibility of using electron accelerator for medical isotope production. JINR Russia, PTI Kharkov Ukraine NEEL Idaho USA YerPhi Yerevan Armenia.

99mTc 123I, 225Ac, 236Pu, SPECT Isotopes and 11C, 13N, 15O, 18F PET

isotopes could be produced by n reaction on electron accelerator.Neutron beam for neutron boron therapy also could be produced on electron accelerator.

Experiments have been performed to verify the technical feasibility of the production and assess the efficiency of the extraction processes.


• Technetium-99 can be obtained in the course of photonuclear processes with 100Mo used as a target according to following reaction:

Threshold of reaction- 9.1 MeV

+ 100Mo99Mo+ n

T1/2 = 67 hours 99mTc (T1/2 =6 hours)


Production Quantity

Appropriate doses of 99mTc vary according to the specific application, but the average dose of the 17 million scans administered each year in the United States is ~ 20 mCi. Thus, the total amount of 99mTc annually administered in the United States is ~ 350000 Ci. Because 99mTc decays so rapidly, a substantial portion of the total production quantity is lost before it can be administered. The extent of this loss depends on the timing of delivery and utilization of the product and on how well matched are the actual and anticipated utilization. Any system that supplies 99mTc must produce sufficient 99Mo to allow for attendant losses inherent in its processes.


Purity Requirements

The currently available products are routinely much purer than the US Pharmacopeia (USP) standards. To succeed in the market place, a new source of 99mTc will have to meet or improve on the following customer expectations:

1. Radiopurity ~ 100 times better than USP requirements 2. Activity concentration 100 to 500 mCi 99mTc per milliliter of eluate3. “Cold” 99Tc/ 99mTc ratio of ~ 4 to 20 at the time of injection4. Total (i.e., radioactive plus nonradioactive) molybdenum concentration comparable to or lower than that in the current product (~ 10-5 g Mo per milliliter of eluate).


Electron Accelerator Parameters:Beam power 20 kWElectron energy 40 MeVElectron beam diameter 4 mmYearly production of 99mTc 20000Ci


Iodine-123 production method

Recently another iodine isotope 123I was produced in several countries. It is short-lived and radiates only and X-rays, which decreases 100 fold the dose of radiation to which patients are exposed. The indication of high quality of the product of 123I is small content of isotopes 124I and 125I.

The isotope 124I radiate high energy gamma deteriorate the solution of scintiograph. The long lived isotope 125I radiates soft and less penetrating radiation and increases the dosage of radiation.


Production of Iodine-123 at some Accelerators

City, Country Particles,

E

Reaction Target Activity

mC

Vancouver, Canada

p, 482 MeV,

10 A

137Cs (p,2p9n) 123Xe

123Xe (E.C.) 123I0.9kg, met. Cs

76mmX100mm 1000

Karlsruhe,

Germany

p, 26 MeV,

15 A

124Te (p,2n) 123I 450mg/cm**2, TeO2,enriching,

124Te 96.5%

400

Davis, USA p, 66 MeV,

20 A

127I (p,5n) 123Xe

123Xe (E.C.) 123I

melted 200-300

Rossendorf,

Germany

d, 14 MeV,

10 A

122Te (d,n) 123I 70mg/cm**2, TeO2, 3cm**2

enriching,124Te 87%

30


The most pure isotope of 123I is believed to be produced during following reaction:

Threshold of reaction – 8.3 MeV

+ 124Xe 123Xe+ n

T1/2 = 2.2 hours 123Xe 123I (T1/2 =13.3 hours)


The effective cross-section for energy of photons about 15 MeV have a maximum equal 450 mbarn. The width of the excitation curve is about 5 Mev. The yield of 123I can exceed 200 Ci/ A*h*gram of 124 Xe. Investigations performed in JINR (Dubna, Russia) for 10g of pure 124Xe irradiated in the course of 8 hours by electron beam with energy of 25 MeV and current of 20 A, give 200mCi activity of 123I . In case of 500MkA daily activity of 123I will be 5 Ci.


How Good is Electron Accelerator for Therapy.

Production of micro-sources for brachy-therapy is also important and this is a very efficient therapeutic method against cancer of the prostate gland

Demand for radionuclides that generate particles with limited track length and large energy of ionization . They can be used in initial stages of lung cancer, leukemia and others.

One of these isotopes is bismuth 213Bi. The need for these isotopes is very large.


213Bi originates during the decay of actinium 225Ac. The following three new approaches could be used for 225Ac production:

-Using Cyclotron proton beam through the reaction 226Ra(p,2n)225Ac

-Using photon beam of linear electron accelerator through reaction 226Ra(,n) 225Ra/225Ac

-Triple neutron capture in 226Ra leading to the production 225Ac/ 213Bi .


Ac-225 Production: Traditional Method

232Th (n; , 2) 233U :This is the current method and involves bombarding Th-232 with thermal neutrons to produce U-233, which will then follow the U-233 decay chain leading to Ac-225. However, the U-233 must be aged ~20 years to produce sufficient Th-229 for efficient extraction.



An efficient method for production of Ac-225 would use a high current electron accelerator to drive the photonuclear reaction

226Ra + 225Ra + n.

The reaction threshold is of 6.4 MeV, the cross section of the reaction increases up to a maximum of 532 mb at an energy 13.75 MeV. Produced after irradiation Ra-225 will be at a maximum and will decay slowly over time, the half-life being 14.9 days, producing Ac-225 by beta emission:

225Ra 225Ac + e-

With the use of electron linear accelerator it is possible to produce isotope Ac-225 in commercially-relevant amounts suitable for medical application.


On Electron Accelerator It is also possible to create neutron beam using gamma neutron and gamma fission reaction. Energy spectra and yeild of neuton

Picted.

Boron neutron capture therapy (BNCT)

Boron neutron capture therapy is very appealing due to its potential for selective cell killing. This therapy is being investigated for several types of cancers including melanoma and glioblastoma multiforme, a highly malignant and therapeutically persistent brain tumour, for which conventional therapies like chemotherapy, surgery, and radiotherapy are not successful.

.The 10B(n,) 7Li reaction has large cross section for thermal neutrons. A boronated compound such as K2B12H12 is injected into the synovial membrane of the diseased knee, which is then exposed to a low-energy neutron beam. 10Boron atoms undergo fission reactions release high-linear-energy-transfer alpha particles and lithium nuclei, which deposit their energy locally (typically 2,3 to 2,8 MeV within 4 to 9 m) damaging or killing cells along their paths. The dose to the synovium is significantly enhanced by the higher concentration of 10B in the synovium.




Boron neutron capture synovectomy for the treatment of rheumatoid arthritis,

New ConceptEconomics

A system based on electron accelerator technology enables the economical supply of 99mTc for a large nuclear pharmacy. Twenty such production centers distributed near major metropolitan areas could produce the entire US supplied of 99mTc at a cost less than the current subsidized price.

Fixed costs CapitalFacility (1600 ft2) $1040000Laboratory equipment 345000Accelerator 2000000Target inventory 450000 Total capital $3715000

Variable costs per yearCost of capital(20%/yr) $745000Salaries (six technicians) 355000Utilities 65000Maintenance and repair 35000Supplies and services 100000Total variable $1300000Yearly production of 99mTc 20000Ci,

New ConceptAdvantages

Production medical radionuclides on electron accelerators offers clear improvements over the current technology in environmental impact, economics, and reliability of supply. Only small amounts of radioactive by-products are produced in this process, and it is not necessary to remove them from the recyclable 100Mo target material.

Environmental

Security

Reliability and Availability

Economics

Purity

Next Step

• Need Collaboration for design and

building the prototype of electron accelerator with mentioned parameters and all other complementary system for turn-key equipment for production mentioned list of Isotopes.

• Collaboration could involve: SNAL. DESY.

NEEL. Triumf. YerPhi.



New concept, electron accelerators, feasibility, advantages

Next steps

Agenda

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Medical Radionuclides