Elsevier

Peptides

Volume 19, Issue 3, 1998, Pages 585-592
Peptides

Articles
(Arg15, Arg21) VIP: Evaluation of Biological Activity and Localization to Breast Cancer Tumors

https://doi.org/10.1016/S0196-9781(97)00459-2Get rights and content

Abstract

Moody, T. W., J. Leyton, E. Unsworth, C. John, L. Lang and W. C. Eckelman. (Arg15, Arg21) VIP: Evaluation of biological activity and localization to breast cancer tumors. Peptides 19(3) 585–592, 1998.—VIP analogs, which contain a single lysine amino acid, were synthesized and evaluated using breast cancer cells. (Arg15, Arg20) VIP, (Arg15, Arg21) VIP, and (Arg20, Arg21) VIP inhibited 125I-VIP binding 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 (Arg15, Arg21) VIP was the most potent at elevating cAMP, it was characterized further. (Arg15, Arg21) VIP transiently increased c-fos gene expression in breast cancer cells. N-Succinimidyl-4-18F (fluoromethly) benzoate was prepared in one chemical step from N-succinimidyl-4-(4-nitrobenzenesulfonyl)oxomethyl)benzoate by adding 18F in acetone at room temperature. This prosthetic group was then reacted with (Arg15, Arg21) VIP ((RR) VIP). (18F-RR) VIP bound with high affinity to T47D cells and was rapidly internalized. (18F-RR) VIP was injected intravenously into nude mice bearing breast cancer xenografts and after 4 h, the density of (18F-RR) VIP was elevated in the tumors relative to normal organs. These data suggest that VIP receptors may be used to localize breast cancer tumors.

Section snippets

Method

MCF-7 and T47D breast cancer cells were purchased from American Type Culture Collection (Rockville, MD) and cultured in DMEM containing 10% heat inactivated fetal bovine serum. The cells were cultured in 5% CO2/95% air at 37°C and were used in exponential growth phase. Routinely the cells, which are adherent, were split 1/10 weekly. VIP, VIPhybrid, and PACAP-27 were purchased from Peninsula Laboratories (San Carlos, CA).

For receptor binding studies, T47D cells were rinsed three times in SIT

Results

The ability of the VIP analogs to bind to T47D cells was determined. Fig. 1 shows that specific 125I-VIP binding was inhibited in a dose-dependent manner by VIP. Little specific binding was inhibited by 0.1 nM VIP, whereas almost all specific binding was inhibited by 1 μM VIP. Specific 125I-VIP binding was half maximally inhibited (IC50) by 0.6 nM VIP. Similarly, (Arg15, Arg21) VIP, (Arg20, Arg21) VIP, and (Arg15, Arg20) VIP had IC50 values of 0.8, 0.7, and 1.2 nM, respectively. Total binding

Discussion

Previously, 111In-octreotide has been used to localize gastrointestinal endocrine tumors using SPECT techniques [22]. This somatostatin agonist is not suitable for localizing breast tumors as only 50% of the breast specimens examined bind somatostatin with high affinity. Recently, it was found that all breast tumors examined bound VIP with high affinity 23, 29. Here, breast tumors were localized using radiolabeled (Arg15, Arg21) VIP.

123I-VIP was used to localize endocrine tumors in the

Acknowledgements

The authors thank Amy Guzzone for technical assistance.

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