Cerebral dopaminergic neurotransmission has been implicated in the etiology or pathogenesis of schizophrenia, affective disorders, tardive dyskinesia, and Parkinson's disease. To study these neuropsychiatric disorders and the related mechanisms of dopamine D2 receptors, several radioiodinated ligands have been developed. Substituted benzamides, in particular, have received significant interest because of their selective, high affinity and the reversible nature of their binding at D2 receptor sites. For example, in vivo rodent striata (a region having many dopamine receptors) to cerebellum (a region having few dopamine receptors) uptake ratios of epidepride and ioxipride have been measured to be 234:1 and 65:1, respectively. The objective of this proposal is the development of cost-effective imaging technology, both hardware and software, for regional imaging of the brain that can provide quantitative measures of regional brain function. The proposed research is the design, construction, and testing of an imager that has a pair of small (75mm x 75mm field of view) gamma cameras for conjugate imaging of distributions of iodinated benzamides in vivo in humans and other primates and the development of image-acquisition and image-analysis software that will make possible the measurement of the radioligand concentrations and of displacement kinetics in various regions of interest. Proposed scientific and engineering efforts include: (i) performance of computer simulations and laboratory experiments to study fundamental aspects of scintillation-crystal/photomultiplier-tube physics; (ii) design, fabrication, and testing of camera mechanical and electronic components; (iii) development of photoevent position-estimation methods and camera-calibration software; (iv) design and construction of a transport cart and camera support structure; (v) development of image-acquisition, image-display, and image-analysis software; and (vi) laboratory experiments using phantoms to characterize the proposed cameras and system. The simultaneous dynamic acquisition of conjugate images will allow for the derivation of effective dose measurements (ED50) of various therapeutic drugs from displacement curves obtained from region-of-interest analysis of acquired images. The clinical usefulness of such analysis has been established using emission computed tomography; however, the proposed small gamma-ray imaging system will be highly cost effective, functionally effective in its selective use, and amenable to broad clinical application.
