About the Group

The following is an overview of the group. Use the related links on the right to view specific information about the group.

Neurology

The Pacific Parkinson's Research Centre at UBC is headed by Dr. Jon Stoessl. The Centre is studying the origins, progression and treatment of Parkinson's disease. In addition to his PET interest, Dr. Stoessl also has an active basic science program studying the mechanisms of therapeutic strategies. The PET investigations are conducted with a wide range of tracers designed to probe the pre- and postsynaptic dopaminergic system. The Centre operates a movement disorder clinic where full assessment of disease severity includes clinical rating scales and video taping of the patients. The Centre is set up to perform clinical trials with pharmaceuticals.

PET Physics Program

Dr. Vesna Sossi heads the physics program, which focuses on the development of algorithms for quantification and reconstruction of data acquired in 3D mode. In May 2003, the group received two new scanners, the High Resolution Research Tomograph (HRRT) and the microPET, which is used to scan rats.

Cyclotron and Pipeline

The TRIUMF cyclotron and chemistry labs are located some 3 km from the University Hospital where the tomograph is located. There is an underground pipeline connecting the 2 sites which enables us to send the prepared radiopharmacueticals to the hospital in under 2 minutes (we have performed [O-15]water studies in a number of protocols using the pipeline).The PET group has a dedicated cyclotron, the TR13, which was designed and built through a collaboration and technology transfer agreement between TRIUMF and EBCO Technologies of Richmond, BC. The TR13 is a negative ion machine that can extract two simultaneous beams of 13 MeV protons with varying beam currents up to 50 A (over 100 A in each beam is possible). There is a target changer with four target positions on each beam line. The targets that are in routine use include those to produce [C-11]CO2, [C-11]methane, [F-18]fluoride and [F-18]fluorinevia with the double shoot method. We also have access to the MDS Nordion CP-42 where there is an [F-18]fluorine target. Solid target irradiations can be performed on the CP-42. We have built a gas phase methyl iodide system for preparing high specific activity (SA) C-11 labeled radiopharmaceuticals and typically achieve SA over 2000 mCi/mole ([C-11]raclopride has been prepared with SA >10Ci/mole). We have also set up the system to prepare tracers of varying SA for performing Scatchard type analyses, in vivo.

Modeling

Through a collaboration with Dr. James Holden of the University of Wisconsin, Dr. Sossi has developed and implemented a number of methods for analyzing our tracer studies,including FDOPA uptake using arterial and cortical input functions, and multi-compartmental and distribution volume determinations for the receptor tracers. In addition we have developed a method for determining the leak rate of FDOPA in long duration scans. We also have SPM and a number of statistical correlation programs developed locally, as well as having locally implemented co-registration programs for intra- and inter-modality studies. We perform metabolite studies on all protocols that require a corrected plasma input function. We have begun studies whereby raclopride is displaced with a dopamine agonist. We have also implemented methods for performing Scatchard analyses using raclopride and Sch23390.

Collaborations

The PET group has close collaborative links with the Chemistry, Physics, Chemical Engineering, Computing, and Pharmaceutical Sciences Departments on the UBC campus, the Chemistry and Computing Science Departments at Simon Fraser University, the Chemistry and Physics Departments at the University of Victoria, and local hospitals including Vancouver General Hospital, Children's Hospital, Lion's Gate Hospital and the BC Cancer Agency.

Significant Findings

Using [F-18]-Fluorodopa, the Group employed PET to detect the occurrence of striatal lesions in subjects who were clinically normal - this was the first direct evidence of preclinical pathology. The discovery shed new insight on pathogenesis, and established a method for identifying preclinical nigrostriatal damage. In PET studies combined with postmortem analysis the Group was the first to demonstrate a direct linear correlation between the indices of fluorodopa (FD) uptake and nigral dopaminergic cell counts, thereby providing a firm basis for in vivo quantification of pathology in the nigrostriatal system. This work was predicated upon the development of a graphical method for analysis of FD PET to generate a striatal uptake constant, which was also accomplished by the group.

Radiochemistry

Dr. Michael Adam is head of the Radiopharmaceutical Chemistry group at TRIUMF. Salma Jivan is responsible for routine production and for development of new techniques. The chemistry group routinely prepares [F-18]FDG, [F-18]FDOPA, [C-11]raclopride for D2 studies, [C-11]SCH23390 for D1, [C-11]dihydrotetrabenazine for the VMAT2, [C-11]methylphenidate for DAT and [F-18]Setoperone for 5HT2. We also produce [C-11] PMP and PK11195. Automated systems are in use for the FDG and FDOPA syntheses. We have developed an automated version of the gas phase methyl iodide system for the [C-11]-labeled tracers. An active program explores the development of transducers for the feedback controls required in automation. Dr. Adam has a research interest in fluorine labeling of carbohydrates using both electrophilic and nucleophilic species. He has close collaborative relationships with the Chemistry Department on the UBC campus.

Instrumentation

The ECAT 953B was installed in 1991. This tomograph has full 3D acquisition capability enabling us to perform multiple studies with minimal radiation exposure to the subjects.Through a Canadian Foundation for Innovation (CFI) grant in conjunction with a BC Knowledge Development Fund grant, we have purchased a new High Resolution Research Tomograph from CTI PET Systems. This brain scanner has approximately 2 mm resolution with depth encoding LSO crystals. We also have a CFI award for the purchase of a dedicated small animal PET camera (microPET) which will be used in rodent models of disease as well as tracer development.

Psychiatry

Dr. Lakshmi Yatham is studying schizophrenia and mood disorders using dopamine tracers and various serotonin receptor antagonists to assess the effect of a number of pharmaceutical interventions.

Research

The major hypotheses that underpin our research efforts concern the etiopathogenesis of diseases of the dopamine and serotonin systems. Research techniques employed by the Group include positron emission tomography, autoradiography, immunohistochemistry, molecular biology, experimental surgery, and epidemiology. All of these are integrated in a setting where a major effort is invested in clinical expertise, so that carefully characterized patients from the Movement Disorders, Schizophrenia, and Mood Disorders Clinics have the opportunity to participate in research. To assist in modeling aging and disease we make extensive use of a colony of non-human primates.

History

The PET Program in Vancouver was established in 1980 as a collaboration between several departments within the Faculty of Medicine at the University of British Columbia and TRIUMF, Canada's National Laboratory for Nuclear and Particle Physics. The program is dedicated to basic research in neurology and psychiatry.

Publications

The group publishes in a multidisciplinary array of journals such as Journal of Nuclear Medicine, Synapse, and Journal of Cerebral Blood Flow & Metabolism, among others.