title: Iodinated PK 11195 as an ex vivo marker of neuronal injury in the lesioned rat brain.
abstract: In order to study the potentials of indirect and direct detection of neuronal damages in humans by single photon emission computerized tomography (SPECT), we compared ex vivo cerebral biodistribution of [125I]PK 11195 with that of [125I]TISCH in a rat model of unilateral striatal excitotoxic lesion. Experiments on in vitro binding with [3H]PK 11195 as a ligand for peripheral type benzodiazepine binding sites (PTBBS) and [3H]SCH 23390 as a ligand for dopamine D1 receptors were also performed to validate our experimental model. We observed a very high increase in the PTBBS and a dramatic decrease in the D1 receptors on the lesioned striatum compared to the intact side. Moreover, we showed that [125I]PK 11195 bound specifically to PTBBS in lesioned cerebral areas ex vivo 5 days after striatal infusion of quinolinic acid (600 nmoles). Increases of 192%, 168%, and 30% were obtained in the striatum, the cortex, and the hippocampus, respectively, on the lesioned side. These results showed that iodinated PK 11195 bound specifically to PTBBS ex vivo and that this binding was dramatically increased at the sites of brain lesion. This ligand could therefore be suitable to detect brain injuries in humans by SPECT, complementing the information given by ligands which image loss in a specific neuron population.
authors.affiliation: INSERM U316, Laboratoire de Biophysique médical et pharmaceutique, Tours, France.
authors.forename: S
authors.initials: S
authors.lastname: Chalon
authors.forename: C
authors.initials: C
authors.lastname: Pellevoisin
authors.forename: S
authors.initials: S
authors.lastname: Bodard
authors.forename: M P
authors.initials: MP
authors.lastname: Vilar
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 / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D007457:Iodine Radioisotopes / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001552:Benzazepines; D007457:Iodine Radioisotopes; D007546:Isoquinolines; C037850:PK 11195