Vasoactive intestinal peptide receptor-based imaging and treatment of tumors

Abstract

Vasoactive intestinal peptide receptors (VIPRs) are members of the G-protein-coupled receptor superfamily. These receptors are overexpressed in many common malignant tumors and play a major role in the progression and angiogenesis of a number of malignancies. Therefore, VIPRs may be a valuable target for the molecular imaging of tumors and therapeutic interventions. The specific natural ligand or its analogs can be labeled with a radionuclide and used for tumor receptor imaging, which could be used to visualize VIPR-related surface protein expression in vivo and to monitor the in vivo effects of molecular drugs on tumors. Moreover, the involvement of VIPRs in malignant transformation and angiogenesis renders them potential therapeutic targets for cancer treatment. A variety of VIP antagonists and cytotoxic VIP conjugates have been synthesized and evaluated for VIPR-targeted molecular therapy. The importance of VIPRs in tumor biology and the ability to predict responses to targeted therapy and monitor drug interventions suggest that VIP receptor-based imaging and treatment will be critical for the early diagnosis and management of cancer. Here, we review the current literature regarding VIPRs and their natural ligands and the involvement of VIPRs in tumor growth and angiogenesis, with an emphasis on the present use of VIPRs for the molecular imaging of tumors and therapies targeting VIPRs.

Atypical nuclear localization of VIP receptors in glioma cell lines and patients

“…The overexpression of these receptors and their involvement in the progression of a number of cancer types and in tumor angiogenesis, have been extensively demonstrated. Consequently, strategies aiming to target these receptors for tumors imaging or therapy are under consideration [11]. An atypical nuclear localization of VIP receptors has been reported in a human colonic adenocarcinoma cell line [12] and VPAC1 nuclear receptors have been observed in human breast cancer [13] and renal carcinoma [14] cells.…”

Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer

“…VIP-immunoreactivity(VIP-IR) occurs in a number of tumors[45•] and VPAC1 is overexpressed, resulting in high densities, in numerous cancers including bladder, breast, colon, liver, lung, pancreatic, prostate, thyroid and uterus- cancer[39, 45•, 46, 47••, 48]. In contrast, VPAC2 has been less well-studied, but is present in gastric leiomyomas; thyroid, gastric/pancreatic adenocarcinomas; lung-tumors, various sarcomas and neuroendocrine-tumors[46, 48-50].…”

“…A similar approach is being investigated for number of tumors(breast, prostate, etc.) overexpressing other GPCR's(bombesin, chemokine, gastrin, etc)[68-71] including VPAC-overexpressing-tumors(especially breast, prostate) using various radiolabeled-VIP analogues[39, 47••, 72, 73]. Recent studies report successful tumor-localization using various radiolabeled-VIP-analogues for experimental studies in animals for cancers of colon [74-76], prostate[77] and breast [78].…”

Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates

“…[ 12 ] The natural ligand VIP and its analogs are investigated for the preparation of drug conjugates. [ 55,56 ] The neurotensin receptor 1 (NTSR1) was found to be overexpressed in a number of different cancer subtypes including breast, colon, pancreatic, lung, and prostate cancer. [ 57 ] For drug delivery, the short hexapeptide neurotensin(8‐13) can be used as carrier with high selectivity and affinity for the NTSR1.…”