(ARG(15),ARG(21))VIP - EVALUATION OF BIOLOGICAL-ACTIVITY AND LOCALIZATION TO BREAST-CANCER TUMORS

VIP analogs, which contain a single lysine amino acid, were synthesize d and evaluated using breast cancer cells. (Arg(15), Arg(20)) VIP, (Ar g(15), Arg(21)) VIP, and (Arg(20), Arg(21)) VIP inhibited I-125-VIP bi nding to T47D cells with high affinity (IC50 values of 1.2, 1.0, and 0 .8 nM, respectively). The VIP analogs elevated cAMP in T47D cells with ED50 values ranging from 0.1-1 nM. Because (Arg(15), Arg(21)) VIP was the most potent at elevating cAMP, it was characterized further. (Arg (15), Arg(21)) VIP transiently increased c-fos gene expression in brea st cancer cells. N-Succinimidyl-4-F-18 (fluoromethly) benzoate was pre pared in one chemical step from midyl-4-(4-nitrobenzenesulfonyl)oxomet hyl)benzoate by adding F-18 in acetone at room temperature. This prost hetic group was then reacted with (Arg(15), Arg(21)) VIP ((RR) VIP). ( F-18-RR) VIP bound with high affinity to T47D cells and was rapidly in ternalized. (F-18-RR) VIP was injected intravenously into nude mice be aring breast cancer xenografts and after 4 h, the density of (F-18-RR) VIP was elevated in the tumors relative to normal organs. These data suggest that VIP receptors may be used to localize breast cancer tumor s. (C) 1998 Elsevier Science Inc.