title: A malignant melanoma imaging agent: synthesis, characterization, in vitro binding and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide.
abstract: In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized 125I-and 131I-labeled (2-piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In vitro homologous competition binding studies of [125I]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma.
authors.affiliation: George Washington University Medical Center, Washington, DC.
authors.forename: C S
authors.initials: CS
authors.lastname: John
authors.forename: W D
authors.initials: WD
authors.lastname: Bowen
authors.forename: T
authors.initials: T
authors.lastname: Saga
authors.forename: S
authors.initials: S
authors.lastname: Kinuya
authors.forename: B J
authors.initials: BJ
authors.lastname: Vilner
authors.forename: J
authors.initials: J
authors.lastname: Baumgold
authors.forename: C H
authors.initials: CH
authors.lastname: Paik
authors.forename: R C
authors.initials: RC
authors.lastname: Reba
authors.forename: R D
authors.initials: RD
authors.lastname: Neumann
authors.forename: V M
authors.initials: VM
authors.lastname: Varma
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006801:Humans; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D001549:Benzamides; D010880:Piperidines; C066918:N-(2-(diethylamino)ethyl)-4-iodobenzamide; C084662:4-iodo-N-piperidinoethylbenzamide