Comparison of three 18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography.
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 [18F]spiroperidol or [18F]benperidol may be suitable for specific labeling of neuroleptic receptors. In an 8-h study with [18F]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. [18F]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 18F in plasma after injection of [18F]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 [18F]spiroperidol remains unchanged after 4 h.
Arnett
C D
CD
Shiue
C Y
CY
Wolf
A P
AP
Fowler
J S
JS
Logan
J
J
Watanabe
M
M
D000818:Animals; D001544:Benperidol / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002069:Butaclamol / Q000494:pharmacology; D002090:Butyrophenones / Q000378:metabolism*; D005260:Female; D005461:Fluorine; D006220:Haloperidol / Q000378:metabolism*; D007553:Isotope Labeling; D008297:Male; D010215:Papio; D011868:Radioisotopes; D051381:Rats; D013134:Spiperone / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002090:Butyrophenones; D011868:Radioisotopes; D005461:Fluorine; D013134:Spiperone; D001544:Benperidol; D002069:Butaclamol; D006220:Haloperidol