TY - JOUR
T1 - Specific, reversible binding of [18F]benperidol to baboon D2 receptors
T2 - PET evaluation of an improved 18F-labeled ligand
AU - Moerlein, Stephen M.
AU - Perlmutter, Joel S.
AU - Welch, Michael J.
N1 - Funding Information:
drophilic byproducts are not expected to partition into the brain. This characteristic is not shared by the [‘XF]fluoroethyl derivative of the ligand, which is metabolized to both lipophilic and hydrophilic compounds (Moerlein and Perlmutter, 1992). A further application of this radioligand is as a means for PET estimation of the central pharmacokineticso f benperidol. Since the mechanism of action of antipsychotics is believed to involve binding to cerebral dopaminergic D, receptors (Creese et al., 1976; Seeman et al., 1976), the determinationv ia PET of the amount of [lXF]BP in D, receptor-richt issue gives a direct measure of the concentrationo f the drug at its targets ite. The use of [“F]BP and PET in this manner would be a unique clinical tool for optimization of pharmacotherapys, ince there is generally poor correlation between clinical response and plasma concentrationso f neuroleptic drugs (Rivera-Calimlim and Hershey, 1984). To summarize, [‘sF]BP is a unique fluorine-18 labeled radiopharmaceuticalf or PET investigation of cerebral dopaminergicD , receptorsi n vivo. The half-life of this radiotraceri s convenient for imaging, synthetic,a nd analytical procedures,t he radioligand rapidly distributes to D, sites of the brain in vivo, and [‘sF]BP is metabolized in the periphery predominantlyt o polar metabolites that are not expected to cross the blood-brain barrier. This work supplementse arlier investigations (Amett et al., 1985) to show that the radiotracerb inds in vivo specifically to D, receptors sites, and not to S, or D, receptors, and that this binding occurs in a reversible manner which is amenable to evaluation of unlabeled drugs that act upon central D, receptors.[ lXF]BP holds promise for PET application with human subjects for examination of pathological conditions as well as for evaluation of pharmacotherapyi n viva Acknowledgements-We thankL . Lich and J. Carl for expert technicala ssistancew ith the animal studiesJ,. Hood and J. Giovanni for datap rocessinga, nd W. Margenaua nd J. Rob-ison for radioisotoppe roductionT.h is work was supportedb y NIH FIRST Award lR29N526788( S.M.M.), NIH Grants R01NS31001R, OlNS32318a ndH L13851a, s well as theg en-erouss upporto f the Dana Foundationt,h e McDonnellC enter for the Study of Higher Brain Function.a nd the GreaterS t. Louis Chaptero f the AmericanP arkinson’sD iseaseA ssocia-tion.
PY - 1995/8
Y1 - 1995/8
N2 - [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner, unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.
AB - [18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner, unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.
UR - http://www.scopus.com/inward/record.url?scp=0029116023&partnerID=8YFLogxK
U2 - 10.1016/0969-8051(95)00022-P
DO - 10.1016/0969-8051(95)00022-P
M3 - Article
C2 - 8535343
AN - SCOPUS:0029116023
SN - 0969-8051
VL - 22
SP - 809
EP - 815
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 6
ER -