RADIOISOTOPE PRODUCTION

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

DiagnosticBeta +

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 99Mo – 99mTc 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 methodHalf-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 particlesCheapest supply of incident particle How can we make an isotope more widely available

New Reactors

Accelerator Approach

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

100Mo(γ,n)99Mo

Proton Machines TRIUMF facility part of the same

commission as CLS Uses ~20MeV Proton Cyclotron Successfully demonstrated the most

favoured approach to accelerator based 99mTc production

100Mo(p,2n)99mTc

TRIUMF Target

Pellet target Target recycling

Low energy accelerators (1) ns-FFAG Ep <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 99Mo/99mTc Production

Direct

100Mo(p,2n)99mTc

98Mo(p,γ)99mTc

Generator

100Mo(p,pn)99Mo

100Mo(p,2n)99mTc 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?

98Mo(p,γ)99mTc

Highest ratio of 99mTc to 99Tc Clean product Very low threshold, only viable for

Ep < 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: 124Te(p,2n)123I

Internal solid powder targetsTargets in both elemental and oxide form

Strontium-87m half-life:2.8hrs Used for bone imaging

Current production: Via generator 87Y (half-life:79.8hrs)

87Sr(p,n)87Y – 87mSr Elemental or compound target (SrCl2)

Ep ~ 20MeV

natRb(a,xn)87YEa < 26MeV

Gallium-67 Half-life: 3.3 days Uses: Long half-life useful for slow

uptake tumour imaging Production: natZn(p,X)67Ga

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: 18O(p,n)18F, 20Ne(d,a)18F,

20Ne(p,2pn)18F Both liquid and gaseous targets used

18O(p,n)18F

Liquid target of H218O housed in a metal

container or gaseous 18O Near threshold proton beam Ep<15MeV F-18 extracted as aqueous fluoride

20Ne(d,a)18F

Gas target of H2Ne so that F-18 is created as H18F 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: 14N(p,a)11C Gas target

Cu-64

Half-life:12.7hrs Uses: joint therapy and diagnostic tool Production: 64Ni(p,n)64Cu, 68Zn(p,an)64Cu Ep ~ 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 68Ge(half-life:270days)

natZn(a,X)68Ge,

natGa(p,X)68Ge

Low energy direct production of 68Ga enriched single isotopic solid target Ep ~ 10MeV 68Zn(p,n)68Ga

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

Summary (2)

Community looking to expand accelerator based methods

Introducing potential new isotopes

Questions?