Background Imaging techniques Reactor production Accelerator production The Moly Crisis Radioisotopes
Historical background Nuclear medicine dates back to as early as the 1800s with the discovery of naturally occurring radioisotopes and the use of x-rays.
Rapid advancements such as the invention of the cyclotron lead to the birth of modern nuclear medicine as we know it today Nuclear reactors also played a role in the development of nuclear medicine as a method of creating radioisotopes
Radioisotopes of all decays alpha, beta and gamma are used for both treatment and diagnostics in nuclear medicine Focus here is on diagnostic isotopes that are either gamma or positron emitters. SPECT or PET Therapy alpha Diagnostic gamma Diagnostic Beta +
SPECT Patients are injected with a gamma emitting isotope attached to a targeting ligand for uptake in specific areas of the body Different length half- lives are suited to different types of procedure e.g. uptake time 2D and 3D maps of an area can be created using a computer model of the signals received.
PET Similar to SPECT but maps created from signals of secondary gammas from positron/e- annihilation
Production methods Once radioisotopes could be manufactured (reactor or accelerator) two different supply methods became available Direct production Generator production
Direct Production The direct production of a radioisotope due to the bombardment of a target isotope by a projectile such as a proton, neutron, alpha or deuteron. The direct production of a radioisotope as a by product of the neutron bombardment inside the target of a research reactor.
Generator production The production of the radioisotope as the decay product of another radioisotope. Most commonly 99 Mo – 99m Tc Parent isotope is collected in a column where the daughter isotope can be eluted using various types of solution dependent on isotope and application. Isotope is then mixed in a pre-prepared kit to form the drug administered to the patient
Rector Production Radioisotopes can also be produced as a by product of spent reactor fuel Currently the most common production route However this supply is under threat due to an aging fleet and no replacements
MOLY CRISIS In 2010 the main reactors went off line for an unexpected extended maintenance. As a result over 80% of the worlds nuclear imaging procedures had to be postponed or cancelled. The current fleet is old and close to retirement with no back up currently in place another crisis is looming
Tc-99m Half-life: ~6hrs, decay: 140keV gamma The most common of the medical radioisotopes primarily due to ease of production Production: Generator via Mo parent – a by product of nuclear reactors Used for a range of SPECT procedures including: bone, brain, blood, lung scans, heart and tumours
Solutions to the crisis New reactors? Accelerators? Current cyclotrons? Linacs? Low energy machines? Other isotopes?
Some factors to consider when determining the most suitable production method Half-life of the isotope in question: is it long enough for direct production, on site or regional supply? Cleanliness of the reaction: how many contaminants are produced alongside the radioisotope of interest and how easily can they be extracted? Natural or enriched targets? How much target material is there? How easily can a target be manufactured and processed? Energy range of incident particles Cheapest supply of incident particle How can we make an isotope more widely available
Solid Targets (1) Thin and thick Foil Elemental or mixed composition typically oxide Created with electroplating
Solid Targets (2) Thick pellet targets Elemental or mixed composition typically oxide Created by compression
Liquid Targets Water or molten metal Compound targets Contained by metal casing often aluminium or nickel Flowing targets aid in cooling
Gas Targets Pressurised gas housed in a metal container
Electron Machines Canadian Light Source part of a commission by the Canadian government to find accelerator methods to replace NRU Uses Bremsstrahlung from an electron linac (35MeV) Principle has been successfully demonstrated 100 Mo(γ,n) 99 Mo
Proton Machines TRIUMF facility part of the same commission as CLS Uses ~20MeV Proton Cyclotron Successfully demonstrated the most favoured approach to accelerator based 99m Tc production 100 Mo(p,2n) 99m Tc
Low energy accelerators (1) ns-FFAG E p <16MeV Can be used with thin or thick targets
ONIAC - Siemens Electrostatic DC accelerator ~10MeV Can be used with thick or thin, solid or liquid targets Proton or deuteron beam Low energy accelerators (2)
Low Energy 99 Mo/ 99m Tc Production Direct 100 Mo(p,2n) 99m Tc 98 Mo(p,γ) 99m Tc Generator 100 Mo(p,pn) 99 Mo
100 Mo(p,2n) 99m Tc Route with the most potential as focus of the TRIUMF studies Cross-section peaks above the energy range of interest for low energy production More efficient at higher energies as proved by TRIUMF is it worth taking forward?
98 Mo(p,γ) 99m Tc Highest ratio of 99m Tc to 99 Tc Clean product Very low threshold, only viable for E p < 5MeV However total yield not large enough for medical quantities
Other SPECT isotopes Iodine-123 half-life:13.2hrs Used for thyroid imaging and treatment Current Production: 124 Te(p,2n) 123 I Internal solid powder targets Targets in both elemental and oxide form
Strontium-87m half-life:2.8hrs Used for bone imaging Current production: Via generator 87 Y (half- life:79.8hrs) 87 Sr(p,n) 87 Y – 87m Sr Elemental or compound target (SrCl 2 ) E p ~ 20MeV nat Rb(a,xn) 87 Y E a < 26MeV
Gallium-67 Half-life: 3.3 days Uses: Long half-life useful for slow uptake tumour imaging Production: nat Zn(p,X) 67 Ga
PET isotopes Typically short-lived positron emitting isotopes Both complimentary and competitive with SPECT
F-18 Half-life: 110mins Uses: brain scans, cardiology and tumour monitoring. FDG the primary F-18 drug Production: 18 O(p,n) 18 F, 20 Ne(d,a) 18 F, 20 Ne(p,2pn) 18 F Both liquid and gaseous targets used
18 O(p,n) 18 F Liquid target of H 2 18 O housed in a metal container or gaseous 18 O Near threshold proton beam E p <15MeV F-18 extracted as aqueous fluoride
20 Ne(d,a) 18 F Gas target of H 2 Ne so that F-18 is created as H 18 F which can be extracted as aqueous fluoride
C-11 Half-life: 20mins Uses: similar to F-18, easily inserted into many biological structures replacing the existing carbon Production: 14 N(p,a) 11 C Gas target
Cu-64 Half-life:12.7hrs Uses: joint therapy and diagnostic tool Production: 64 Ni(p,n) 64 Cu, 68 Zn(p,an) 64 Cu E p ~ 16MeV
Ga-68 Half-life:68mins Uses: similar to F-18 but preferred for areas with high background FDG uptake such as brain tumours Production: currently via generator 68 Ge(half-life:270days) nat Zn(a,X) 68 Ge, nat Ga(p,X) 68 Ge
Low energy direct production of 68 Ga enriched single isotopic solid target E p ~ 10MeV 68 Zn(p,n) 68 Ga
Summary Radioisotopes are a vital life saving tool Many methods of manufacture, the most suitable system is determined by the isotope in question i.e. half-life, contaminants, target material abundance Currently dependent on reactor based methods which lead to supply crisis