Details

Autor(en) / Beteiligte

• Schwartz, Robert A

Titel

In vivo evaluation of the D(1) agonist PET ligand R-[carbon-11]SKF 82957: Metabolism and regional brain distribution in animal models and humans

Ort / Verlag

ProQuest Dissertations Publishing

Erscheinungsjahr

1999

Link zum Volltext

• ProQuest

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Rationale. The dopamine D1 receptor high-affinity (D1HIGH) state is believed to be the functional state of the receptor coupled to the G protein. Only agonist or partial agonist radioligands are capable of discerning the high- and low-affinity state with positron emission tomography (PET), while antagonists cannot. With the use of a selective D1 agonist radioligand, such as R-[11C]SKF 82957, it may be possible to assess changes in the D1HIGH receptor in vivo in human subjects with PET. Objectives. The main objective of this research was to determine the suitability of R-[11C]SKF 82957 for its use in human PET imaging. The metabolism of this radioligand was first ascertained in rat plasma and brain extracts, then in human plasma, with particular attention focused on the possible formation of radiolabeled metabolites with the potential to cross the blood brain barrier. PET imaging was performed in healthy human volunteers, and regional brain uptake and binding potential of striatal R-[ 11C]SKF 82957 was examined. Two rat models of D1 receptor supersensitivity (chronic D1 agonist treatment with SKF 81297 and unilateral 6-hydroxydopamine (6-OHDA) lesions), were tested to establish the in vivo binding of R-[11C]SKF 82957 versus that of [11C]SCH 23390. (Abstract shortened by UMI.)