title: Is TISCH a suitable tracer for in vivo study of modifications of the dopamine D-1 receptor?
abstract: To detect quantitative modification of dopamine D-1 receptors in vivo, we used [125I]-TISCH in an animal modelin which the striatum was unilaterally lesioned with quinolinic acid. [125I]-TISCH was injected into rats 5 days after the lesion, and the changes in receptor density obtained in vivo were compared to in vitro quantification of dopamine D-1 receptors by binding with either [125I]-TISCH or [3H]-SCH 23390 as a reference ligand. In vivo and in vitro, we obtained the same decrease (-70%) in binding of these ligands in the lesioned striatum. Using an injection of [99mTc]-DTPA to lesioned rats, we also showed the disruption of the blood-brain barrier (BBB) in the lesioned area. Thus, the equivalent decrease observed in vitro and in vivo with [125I]-TISCH confirmed that this molecule would be a valuable tool for exploration of dopamine D-1 receptors by SPECT imaging. Moreover, the fact that the breakdown of the BBB did not interfere with the receptor binding obtained in vivo may be important for future investigations in pathologies with BBB disruption, such as ischemia.
authors.affiliation: Inserm U316, Laboratoire de Biophysique Medicale et Pharmaceutique, UFR Des Sciences Pharmaceutiques, Tours-France.
authors.forename: C
authors.initials: C
authors.lastname: Pellevoisin
authors.forename: S
authors.initials: S
authors.lastname: Chalon
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: J C
authors.initials: JC
authors.lastname: Besnard
authors.forename: D
authors.initials: D
authors.lastname: Guilloteau
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000502:physiology; D002614:Chelating Agents; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D007267:Injections; D007457:Iodine Radioisotopes; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism; D016284:Technetium Tc 99m Pentetate
chemical_list: D001552:Benzazepines; D002614:Chelating Agents; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D017447:Receptors, Dopamine D1; C067811:7-chloro-8-hydroxy-1-(3'-iodophenyl)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine; D017378:Quinolinic Acid; D016284:Technetium Tc 99m Pentetate