Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting
Reubi, Jean ; Gugger, Mathias ; Waser, Beatrice
In: European Journal of Nuclear Medicine and Molecular Imaging, 2002, vol. 29, no. 7, p. 855-862
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- Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y1) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC1, GRP and NPY(Y1) receptors using in vitro receptor autoradiography on successive tissue sections with 125I-[Tyr3]-octreotide, 125I-VIP, 125I-[Tyr4]-bombesin and 125I-[Leu31,Pro34]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (<2,000dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y1) receptors, 25 (37%) expressed VPAC1 receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819±530dpm/mg tissue for GRP receptors, 9,135±579dpm/mg for NPY(Y1) receptors, 4,337±528dpm/mg for somatostatin receptors and 3,437±306dpm/mg for VPAC1 receptors. It is of note that tumours expressing NPY(Y1) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y1 analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy