The cyclotron and radiochemistry are major components of the Neuroscience Research Institute's research activity. The Cyclotron and Radiochemistry Team has been continuously and closely working with the PET team, as well as other MRI and micro-animal imaging teams to develop new ligands and contrast agents. Here we present the developments and achievements of the last two years and that we hope will continue.
• Radioisotopes (or radionuclides) and radioligands developed at the Neuroscience Research Institute (2009)
A radionuclide is an atom with an unstable nucleus, i.e. a nucleus characterized by excess energy that is available to be imparted either to a newly-created radioactive particle within the nucleus or to an atomic electron (see internal conversion). In this process, the radionuclide undergoes radioactive decay and emits gamma rays and/or subatomic particles. These particles constitute ionizing radiation. Radionuclides may occur naturally, but they can also be artificially produced.
Radionuclides are often referred to by chemists and physicists as radioactive isotopes or radioisotopes, and they play an important part in the technologies that provide us with food, water, and good health. However, they can also constitute real or perceived dangers.
- [18F] FDG
The most common RP; used for various diagnostic imaging techniques and basic research due to its ability to reflect the plasma glucose metabolism rate
- [11C] Acetate, [11C] Methionine
Brain tumor detection imaging
- [18F] FLT
DNA proliferation detection
• Radiopharmaceuticals (or radiotracers) developed since 2007
A radiopharmaceutical is defined as a substance that is mostly biologically active material (enzyme substrate, receptor ligand, nano-particle, etc.) labeled with a short lived radioisotope (18F, 11C, 99mTc, 123I). The four radiopharmaceuticals listed below are routinely prepared at the Neuroscience Research Institute for preclinical and clinical studies.
- [18F] FDDNP
This is one of the most useful radiotracers used for Alzheimer’s disease (AD) imaging. It shows the in vivo concentration of senile plaques and fibrillary tangles found in AD.
- [11C] PIB
The most popular PET tracer; used to quantify the amyloid load in brains with Alzheimer-type dementia.
- [11C] Raclopride
This tracer can be used to measure the in vivo dopamine receptor occupancy (especially D2), which helps neuroscientists investigate brain diseases and effects of psychiatric drugs in vivo.
- [18F] FP-CIT
Used for dopamine transporter density imaging.
- [11C] Carfentanil
As a µ-opioid agonist, it is used to measure the endogenous release of µ-opioid.
- [18F] MPPF
As a 5-HT 1A receptor antagonist, it is used to measure the endogenous release of 5-HT.
- [18F] Fallypride
Used for the detection of extra-striatal D2 receptor density.
- [11C] PK11195
Used for the detection of microglial activation.
• Cyclotron Facility
Machines and equipment available in the cyclotron facility in NRI are:
1. 11 MeV CTI-SIEMENS dual beam cyclotrons (7 Ci from 2 h with double beam)
2. Dispense/mini/research hot cells
3. FDG full automated synthesis module (Explora FDG4, CTI-SIEMENS)
4. F-18/C-11 multi-purpose radio-synthesis system including HPLC purification
5. C-11 MeI synthesis module (Explora MeI, CTI-SIEMENS)
6. A wide range of equipment for the quality control of radiopharmaceuticals (HPLC, GC, radio-TLC, etc.)
Fig. 1. 11 MeV Cyclotron (left) and FDG automated synthesizer (right)
• Future Research
1. Supplying radiopharmaceuticals for preclinical and clinical research
2. Developing radiotracer synthesis systems for 18F- and 11C-labeled compounds
3. Developing novel synthesis methods for the larger scale production of radiotracers
4. Developing novel radiotracers for the imaging of Alzheimer’s disease
Fig. 2. Multipurpose research module system (left) and diagrams for this system (middle and right)
Fig. 3. Control box circuit diagram
• Research Interests
Development of next generation tracers for Alzheimer’s disease imaging
Development of highly efficient radiolabeling modules for large scale radiopharmaceutical production
Improvement of the specific activity of 11C-labeled radiotracers with “wet chemistry”