BIOLOGICAL IMAGING AND THE MOLECULAR-BASIS OF DOPAMINERGIC DISEASES

The development and validation of preclinical biological probes of nig rostriatal dysfunction are part of the next frontier for battling dise ases involving dopamine deficiency. In this work, the quantitative rel ationship relationship between radiofluorinated L-DOPA, [e.g., L-3,4-d ihydroxy-6-[F-18]fluorophenylalanine (6-[F-18]fluoro-L-DOPA, FDOPA)] k inetics measured with positron emission tomography and central dopamin e biochemistry is discussed. A hypothesis of a possible ''non-linearit y'' of FDOPA kinetics with dopaminergic cell losses is presented to ex plain apparent discrepancies in post-mortem biochemical and histologic al determinations in Parkinson's disease. Similar observations have be en made in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed monkeys and human subjects where the FDOPA uptake constantly fell wit hin normal values unless severe nigral damage had occurred. The limita tions of FDOPA, and other biological probes, for examining the asympto matic phase of dopaminergic diseases and the future direction of resea rch are discussed. (C) 1997 Elsevier Science Inc.