A Malignant Melanoma Imaging Agent: Synthesis, Characterization, In Vitro Binding and Biodistribution of Iodine-125-(2-Piperidinylaminoethyl)4-Iodobenzamide

• Published in: The Journal of nuclear medicine (1978) Vol. 34; no. 12; pp. 2169 - 2175
• Main Authors: John, C.S, Bowen, W.D, Saga, T, Kinuya, S, Vilner, B.J, Baumgold, J, Paik, C.H, Reba, R.C, Neumann, R.D, Varma, V.M, McAfee, J.G
• Format: Journal Article
• Language: English
• Published: United States Soc Nuclear Med 01-12-1993
• Subjects: Animals; Benzamides - chemical synthesis; Benzamides - pharmacokinetics; Chromatography, High Pressure Liquid; Guinea Pigs; Humans; Melanoma, Experimental - diagnostic imaging; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Piperidines - chemical synthesis; Piperidines - pharmacokinetics; Radionuclide Imaging; Tissue Distribution; Tumor Cells, Cultured - metabolism
• ISSN: 0161-5505; 1535-5667

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.