title: Synthesis and evaluation of [123I]-iodo-PK11195 for mapping peripheral-type benzodiazepine receptors (omega 3) in heart.
abstract: An iodinated analog of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide , a specific antagonist of the peripheral-type benzodiazepine receptor (omega 3), has been synthesized in three steps with an overall chemical yield of 40%. Both [123I]- and [125I]-Iodo-PK11195 have been synthesized by solid-state isotopic exchange in > 60% isolated radiochemical yield and specific activity of 233-348 mCi/mmol. Tissue distribution studies in rats indicate a high uptake of radioactivity in adrenal glands, heart, lung and kidneys, which was blocked 63-87% by preadministration of cold PK11195. Single photon emission computer tomography (SPECT) imaging of the canine heart has been accomplished with [123I]PK11195. These results suggest that [123I]PK11195 has potential as a SPECT radiotracer for studying the omega 3 receptor in humans.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Gildersleeve
authors.forename: M E
authors.initials: ME
authors.lastname: Van Dort
authors.forename: J W
authors.initials: JW
authors.lastname: Johnson
authors.forename: P S
authors.initials: PS
authors.lastname: Sherman
authors.forename: D M
authors.initials: DM
authors.lastname: Wieland
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004285:Dogs; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007546:Isoquinolines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195