750,000 Americans suffer from Parkinson's disease. Although the incidence is highest in older adults, the disease may also afflict young adults resulting in significant loss of productivity, major health care expenses, and impairment of the quality of life. New methods of treatment, specifically fetal tissue transplantation, have been proposed and/or carried out. Unfortunately, it is difficult, using existing methods, to quantitatively assess the survival of transplanted tissue, its dopamine production, or the effect of transplantation on host neuronal preservation or restoration. However, within the last two years, a radiolabeled ligand, identified as [123I]beta-CIT(2-beta-Carbomethoxy-3-beta-(4- iodophenyl)tropane, has been demonstrated to be an effective marker of dopamine reuptake sites in the caudate nucleus and the putamen. The current project proposes to answer the following research question: can [123I]beta-CIT be used in conjunction with SPECT imaging to evaluate viability and growth of transplanted tissue or other treatment methods in an animal model of Parkinson's Disease? This work is proposed to be carried out in an MPTP induced primate model of Parkinson's disease.
Specific aims i nclude (1) determination of differences in [123I]beta-CIT clearance characteristics of normal (control) and MPTP treated animals in order to determine the ideal imaging time; (2) the sensitivity of [123I]beta-CIT for detection of changes in dopaminergic reuptake sites as determined by test/retest measurements; (3) determination of effects of both MPTP treatment and subsequent tissue transplant on [123I}beta-CIT localization over a long time period; (4) determination of the relationship among [123I]beta-CIT uptake, behavioral indices of parkinsonism, and direct tissue dopamine concentrations post mortem in MPTP treated and neural transplanted primates. The project will utilize and benefit from the resources of a major neural transplantation program and dedicated primate research facility at the St. Kitts Biomedical Research Foundation. The studies will be performed using a Picker 3000 SPECT imaging device which will be installed at the laboratory in St. Kitts for these studies, replacing the Strichman device which was used for the collection of preliminary data. This study will serve as a useful paradigm for evaluating other methods for restoring brain dopamine systems if and when they become available.
