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Evaluation of 5‐[ 18 F]Fluoropropylepidepride as a potential pet radioligand for imaging dopamine D2 receptors
Author(s) -
Kessler Robert M.,
Votaw John R.,
de Paulis Tomas,
Bingham Daniel R.,
Ansari M. Sib,
Mason N. Scott,
Holburn George,
Schmidt Dennis E.,
Votaw Delicia B.,
Manning Ronald G.,
Ebert Michael H.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890150302
Subject(s) - chemistry , raclopride , dopamine , dopamine receptor d2 , radioligand , striatum , dopamine receptor , receptor , amphetamine , medicine , pharmacology , endocrinology , biochemistry
This study evaluated the utility of (S)‐N ‐[(1‐ethyl‐2‐pyrrolidinyl)methyl]‐5‐(3‐[ 18 F]fluoropropyl)‐2,3‐dimethoxybenzamide ([ 18 F]fluoropropylepidepride), [ 18 F]5‐FPrEpid, as a ligar d for PET studies of cerebral dopamine D2 receptors. The in vitro affinity for the rat striatal dopamine D2 receptor, K D 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal homogenate. The apparent lipophilicity, log k w 1.6, was measured with reverse phase HPLC at pH 7.5. The receptor specificity was determined by competitive displacement of [ 18 F]5‐FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands displaced [ 18 F]5‐FPrEpid with high affinity. Positron tomographic imaging studies in primates of [ 18 F]5‐FPrEpid demonstrated a stable striatal uptake. of 0.02% injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal uptake was displaceable by haloperidol (1 mg/kg) or raclopride (2.5 mg/kg) to cerebellar levels with a t 1/2 of washout of 9 or 15 min. Striatal uptake was mildly susceptible to displacement by d‐amphetamine (1–2 mg/kg) released endogenous dopamine; d‐amphetamine administration produced a 10%/h increase in the rate of striatal washout. Although uptake in the striatum is reversible, an equilibrium between receptor bound [ 18 F]5‐FPrEpid in striatum and [ 18 F]5‐FPrEpid in plasma is not reached within 5 h postinjection. © 1993 Wiley‐Liss. Inc.