title: Radiosynthesis and in vivo evaluation of the pseudopeptide delta-opioid antagonist [(125)I]ITIPP(psi).
abstract: The radioiodinated tetrapeptide delta-opioid antagonist [(125)I]ITIPP(psi) [H-Tyr(3'I)-Ticpsi[CH2NH]Phe-Phe-OH] (Ki(delta) = 2.08 nM; Ki(micro)/Ki(delta) = 1280) has been synthesized and evaluated as a potential lung tumour imaging agent. [(125)I]ITIPP(psi) was obtained, via electrophilic iodination, in 46% yield (>44,000 MBq/micromol) from the parent TIPP(psi). The biodistribution of [(125)I]ITIPP(psi) in nu/nu mice bearing SCLC-SW210.5 xenographs revealed good uptake and prolonged retention of radioactivity in organs known to possess delta-opioid receptors. Metabolite analysis showed that [(125)I]ITIPP(psi) was largely unmetabolized at 25 min PI and blocking studies showed significant reduction of uptake of the tracer in the brain, liver, intestine and tumor indicating that the iodinated tetrapeptide binds to delta opioid receptors in vivo.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. TC311@columbia.edu
authors.forename: T L
authors.initials: TL
authors.lastname: Collier
authors.forename: P W
authors.initials: PW
authors.lastname: Schiller
authors.forename: R N
authors.initials: RN
authors.lastname: Waterhouse
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000000981:diagnostic imaging; D051379:Mice; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D009842:Oligopeptides; D019275:Radiopharmaceuticals; D017465:Receptors, Opioid, delta; C434708:iodo-tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine