NEUROLEPTIC BINDING-SITES - SPECIFIC LABELING IN MICE WITH [18] HALOPERIDOL, A POTENTIAL TRACER FOR POSITRON EMISSION TOMOGRAPHY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 24  (5) , 408-416
Abstract
Haloperidol labeled with 18F (T1/2 [half-life] = 110 min, positron emission 97%), prepared yielding 0.04 Ci/mmol by the Balz-Schiemann reaction, was evaluated in a murine model as a potential radiotracer for noninvasive determination, by positron-emission tomography, of regional concentrations of brain dopamine receptors in patients [with various neurologic disorders]. As the haloperidol dose in mice was increased from 0.01 to 1000 .mu.g/kg, the relative concentration of [18F]haloperidol (.mu.Ci per g specimen/.mu.Ci per g of body mass), at 1 h after injection decreased from 30 to 1.0 in the striatum and from 8.0 to 1.0 in the cerebellum. The striatal radioactivity, plotted as relative concentration against log of dose, decreased sigmoidally, presumably reflecting competition between labeled and unlabeled haloperidol for a single class of accessible binding sites. Because the cerebellum is relatively deficient in dopamine receptors, the observed decrease in cerebellar radioactivity may reflect a saturable component of haloperidol transport into brain. The high brain concentrations and the unexpectedly high striatum-to-cerebellum concentration ratios (> 4 at haloperidol doses .ltoreq. 1 .mu.g/kg) suggest that [18F]haloperidol warrants further investigation as a potential radiotracer for dopamine receptors.