Overview of Cyclotron Facilities

Objective To present an overview of the requirements to establish and operate a cyclotron facility to produce positron emitters, including the accelerator itself and associated systems.

1) The use of radioisotopes produced in accelerators; 2) The production of radioisotopes and types of targets; 3) The cyclotrons; 4) The hot cells; 5) Types of Facilities (I - V); 6) Perspectives

Imaging Radiotherapy Radiotracers The use of radioisotopes produced in accelerators The use of radionuclides in the physical and biological sciences can be divided into three categories: Imaging Radiotherapy Radiotracers TECHNICAL REPORTS SERIES No. 465

3) The tracer concentration can be measured. In order to be used as tracers, the radionuclides and the compounds to which they are attached must obey the tracer principles, which state that: 1) The tracer behaves or interacts with the system to be probed in a known and reproducible fashion. 2) The tracer does not alter or perturb the system in any measurable fashion. 3) The tracer concentration can be measured.

Some typical radionuclides used in imaging Half life Reaction Use 99mTc 6 h 100Mo(p, 2n) 235U(n,f) SPECT 123I 13.1 h 124Xe(p, 2n) 124Xe(p, pn) 124Xe(p, 2pn) 123Te(p, n) 124Te(p, 2n)

Radionuclide Half life Reaction Use 201Tl 73.1 h 203Tl(p, 3n) SPECT 67Ga 3.2 d 68Zn(p,2n) 11C 20.3 min 14N(p,α) PET 18F 110 min 18O(p,n) natNe(d, α) 13N 10 min 16O(p, α) 13C(p, n) 15O 2 min 15N(p, n) 14N(d, 2n) 16O(p, pn)

Functional Information + Anatomic Details

http://www.norcalscans.org

Cyclotrons •••••••••••••••••••••••••••••••••• The production of radioisotopes and types of targets •••••••••••••••••••••••••••••••••• Cyclotrons

Not all radionuclides can be produced in reactors, e.g. 201Tl, 18F, … Many radionuclides are produced in reactors as fission products or through activation, e.g. 99Mo Radio nuclide Reaction Q - value 15O 14N(d,n)15O 1 MeV 18F 18O(p,n)18F 3 MeV 201Tl 203Tl(p,3n)201Pb201Tl 18 MeV 111In 112Cd(p,2n)111In 11 MeV 67Ga 68Zn(p,2n)67Ga 12 MeV Not all radionuclides can be produced in reactors, e.g. 201Tl, 18F, … These can only be produced through threshold reactions with charged particles Hence there is a need for high energy charged particles

Cyclotron characteristics Type of target Yield of the production Choice of nuclear reaction: Cyclotron characteristics Type of target Yield of the production

Reaction mechanism 18O 19F* 18F 8 p - 10 n 9 p - 10 n 8 p - 10 n 1 p

Cyclotron produced Reactor produced

Targets Constitution Shape Choice of target Choice of reaction Direct production Separation of products Quality Control Indirect production Separation of products Targets

Targets solid liquid gas

The target holder must be designed to accommodate the material that is irradiated according to its characteristics and physical state. The main concern in target design is the generation and dissipation of heat. The purpose of the cooling system is to guarantee the integrity of the blank and target holder.

The Cyclotrons

There are many different types of cyclotrons: A cyclotron is a compact electromagnetic device capable of accelerating charged particles to high energies. There are many different types of cyclotrons: A positive ion cyclotron: Proton: 40 MeV, 100 µA Deuteron: 20 MeV, 230 µA Alpha: 40 MeV, 80 µA

A negative ion cyclotron: Proton: 30 MeV, 350 µA Deuteron: 15 MeV, 100 µA

A self-shielded cyclotron: Proton: 11 MeV, 80 µA

Characteristics of cyclotrons Particle type: Light or heavy ions are accelerated Either positive or negative ions are used Most common are protons and deuterons Energy of the particle beam: High energies are achieved Most common are energies between 10 and 30 MeV Cyclotrons with a maximal beam energy of several 100 MeV are available for research purposes and radiotherapy

Characteristics of cyclotrons (cont) Beam current: A beam of charged particles represents an electric current Maximal beam currents of a few 10 µA up to over 1 mA are commercially available Power output: A combination of particle energy and beam current Typically between 1 kW and 10 kW

First Generation: It was not possible to distinguish between commercial cyclotrons and equipment used in research. The Cyclotron Corporation (TCC) and Scanditronix Accelerate protons Internal ion source Local production

CP42 and MC32NI (Scanditronix)‏ Second Generation: In the 70s, the construction of a H- accelerator was proposed. The extraction was very simple, leading to a broad range of possible energies for the beam. CP42 and MC32NI (Scanditronix)‏

Third Generation: Developed based on market expectations and improvements of existing H- cyclotrons.

1968 1975 1984 Cyclotrons for radionuclide production in Germany http://www.hzdr.de 1968 1975 1984 CV 28 Particles and energies: p = 2-24 MeV d = 3-14 MeV 3He2+ = 5-36 MeV 4He2+ = 6-28 MeV Philips 140/IV Particles and energies: p = 4-30 MeV d = 2-16 MeV 3He2+ = 6-42 MeV 4He2+ = 6-36 MeV MC16 Particles and energies: p = 17.2 MeV d = 8.3 MeV 3He2+ = 12.4 MeV 4He2+ = 16.5 MeV CP42H Particles and energies: negative ions p = 15-42 MeV

1993 2000 2008 PETtrace Particles and energies: negative ions p = 16.5 MeV d = 8.4 MeV CYCLONE 18/9Particles and energies: negative ions  p = 18 MeV d = 9 MeV RDS 112 Particles and energies: negative ions p = 11 MeV TR19/9 Particles and energies: negative ions p = 19 MeV d = 9 MeV

Hot Cells

Protons are accelerated Production of 18F Protons are accelerated Hit the target (18O) Interaction with the 18O Neutron emission

The target irradiation with a proton beam produces 18F; Generally, the irradiation takes 2 hours (one half life); FDG 18F is sent to the synthesis module, to react with some components in order to generate the FDG; The synthesis module performs various operations like cooling, filtration, purification, etc. Synthesis: 1 hour

Types of Facilities The appropriate design of the facility is essential to achieve the desired safety and quality for the final product.

Types of Facilities The design is derived, in a large extent, from the application of national (or international) standards and guidelines for the manufacture of radiopharmaceuticals and radiation protection.

The application of access control, interlocks, segregation and pass-through must be integrated into the design of the building, together with the types of structural materials suitable for achieving the objectives of the facility. The design must optimize the flow of materials and people, and integrate structural elements necessary to achieve these objectives.

Facility Type (TRS 471): TYPE I II III IV V  X FDG production Distribution local regular large scale variable Other short-lived radionuclides (11C, 13N, 15O....) X Research extensive program Perform maintenance tasks in the cyclotron Other nontraditional emitters (201Tl, 123,124I, 67Ga, 64Cu....) maybe