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Comparison of Three 18 F‐Labeled Butyrophenone Neuroleptic Drugs in the Baboon Using Positron Emission Tomography
Author(s) -
Arnett Carroll D.,
Shiue ChyngYann,
Wolf Alfred P.,
Fowler Joanna S.,
Logan Jean,
Watanabe Masazumi
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb12891.x
Subject(s) - chemistry , spiperone , baboon , butyrophenone , desmethyl , haloperidol , striatum , in vivo , positron emission tomography , radiochemistry , receptor , endocrinology , metabolite , dopamine receptor , pharmacology , nuclear medicine , dopamine , biochemistry , medicine , biology , microbiology and biotechnology
The butyrophenone neuroleptics spiroperidol, benperidol, and haloperidol were radiolabeled with fluorine‐18 and studied in baboon brain using positron emission transaxial tomography (PETT). Pretreatment of the baboon with a high pharmacological dose of (+)‐butaclamol reduced the specifically bound component of radioactivity distribution in the striatum to approximately the radioactivity distribution found in the cerebellum. Comparative studies of brain distribution kinetics over a 4‐h period indicated that either [ 18 F]spiroperidol or [ 18 F]benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8‐h study with [ 18 F]spiroperidol, striatal radioactivity did not decline, suggesting that spiroperidol either has a very slow dissociation rate or that it binds irreversibly to these receptors in vivo. [ 18 F]Haloperidol may not be suitable for in vivo PETT studies, because of a relatively high component of nonspecific distribution and a faster dissociation from the receptor. Analysis of 18 F in plasma after injection of [ 18 F]spiroperidol indicated rapid metabolism to polar and acidic metabolites, with only 40% of the total radioactivity being present as unchanged drug after 30 min. Analysis of the metabolic stability of the radioactively labeled compound in rat striatum indicated that greater than 95% of [ 18 F]spiroperidol remains unchanged after 4 h.