High affinity dopamine D2 receptor radioligands. 3. [[sup 123]I] and [[sup 125]I]epidepride: In vivo studies in rhesus monkey brain and comparison with in vitro pharmacokinetics in rat brain

Journal Article · Fri Jan 01 00:00:00 EST 1993 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(93)90675-S· OSTI ID:6440042

Kessler, R M; Votaw, J R; Schmidt, D E; Ansari, M S; Holdeman, K P; Paulis, T de; Clanton, J A; Pfeffer, R; Manning, R G; Ebert, M H ^[1]

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1. Vanderbilt Univ., Nashville, TN (United States)

Studies of [[sup 123]I]epidepride uptake in rhesus monkey brain were performed using single photon tomography. Striatal uptake peaked at 0.85% of administered dose/g at 107 min post-injection, then declined slowly to 0.70% of administered dose/g at 6 h. Striatal:posterior brain ratios rose from 2 at 25 min to 6.8 at 105 min, to 15 at 4 h and to 58 at 6.4 h. [[sup 123]I]Epidepride was displaced by haloperidol (0.1 and 1 mg/kg) with a half-life of washout of 55 min. Little displacement of [[sup 123]I]epidepride was observed following administration of 1 or 2 mg/kg d-amphetamine, respectively, indicating [[sup 123]I]epidepride is not easily displaced by endogenous dopamine. In vitro equilibrium binding studies with [[sup 125]I]epidepride using rat striatum revealed a K[sub D] of 46 pM and B[sub max] of 33 pmol/g tissue at 37[degrees]C, while at 25[degrees]C the K[sub D] was 25 pM and the B[sub max] 32 pmol/g tissue. In vitro kinetic analysis of association and dissociation curves revealed a half-life for receptor dissociation at 37[degrees]C of 15 min and 79--90 min at 25[degrees]C. Allowing for the temperature difference, there is good correspondence between in vivo and in vitro dissociation kinetics at 25[degrees]C. Increasing in vitro incubation temperature from 25 to 37[degrees]C caused a 6-fold increase in the dissociation rate, suggesting that there is a change in binding kinetics at the dopamine D2 receptor at 37[degrees]C compared to in vivo binding. The results of this study indicate that [[sup 123]I]epidepride is an excellent radioligand for SPECT studies of the dopamine D2 receptor in man. 34 refs., 4 figs.

• OSTI ID: 6440042
• Journal Information: Life Sciences; (United States), Vol. 53:3; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
DOPAMINE
BIOMEDICAL RADIOGRAPHY
LIGANDS
BINDING ENERGY
KINETICS
RADIOPHARMACEUTICALS
RECEPTORS
AMIDES
BENZENE
CHEMICAL PREPARATION
CONTRAST MEDIA
IN VITRO
IN VIVO
IODINE 123
IODINE 125
PYRROLIDINES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BETA DECAY RADIOISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENERGY
HETEROCYCLIC COMPOUNDS
HOURS LIVING RADIOISOTOPES
HYDROCARBONS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MEDICINE
MEMBRANE PROTEINS
NEUROREGULATORS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
PYRROLES
RADIOISOTOPES
RADIOLOGY
SYMPATHOMIMETICS
SYNTHESIS
550601* - Medicine- Unsealed Radionuclides in Diagnostics
400703 - Radiochemistry & Nuclear Chemistry- Radioisotope Production