Peptide hormone receptors overexpressed in human tumors, such as somatostatin receptors, can be used for in vivo targeting for diagnostic and therapeutic purposes. A novel promising candidate in this field is the GLP-1 receptor, which was recently shown to be massively overexpressed in gut and lung neuroendocrine tumors-in particular, in insulinomas. Anticipating a major development of GLP-1 receptor targeting in nuclear medicine, our aim was to evaluate in vitro the GLP-1 receptor expression in a large variety of other tumors and to compare it with that in nonneoplastic tissues. Methods: The GLP-1 receptor protein expression was qualitatively and quantitatively investigated in a broad spectrum of human tumors (n 5 419) and nonneoplastic human tissues (n 5 209) with receptor autoradiography using 125 I-GLP-1(7-36)amide. Pharmacologic competition experiments were performed to provide proof of specificity of the procedure. Results: GLP-1 receptors were expressed in various endocrine tumors, with particularly high amounts in pheochromocytomas, as well as in brain tumors and embryonic tumors but not in carcinomas or lymphomas. In nonneoplastic tissues, GLP-1 receptors were present in generally low amounts in specific tissue compartments of several organs-namely, pancreas, intestine, lung, kidney, breast, and brain; no receptors were identified in lymph nodes, spleen, liver, or the adrenal gland. The rank order of potencies for receptor binding-namely, GLP-1(7-36)amide 5 exendin-4 GLP-2 5 glucagon(1-29)-provided proof of specific GLP-1 receptor identification. Conclusion: The GLP-1 receptors may represent a novel molecular target for in vivo scintigraphy and targeted radiotherapy for a variety of GLP-1 receptor-expressing tumors. For GLP-1 receptor scintigraphy, a low-background signal can be expected, on the basis of the low receptor expression in the normal tissues surrounding tumors. G protein-coupled peptide hormone receptors play an increasing role in cancer medicine. This role is based primarily on the peptide receptor overexpression on tumor cells, which allows specific receptor-targeted scintigraphic tumor imaging and tumor therapy with radiolabeled peptide analogs (1). The somatostatin receptors were the first peptide receptors identified for these purposes, and somatostatin receptor targeting has now become an integral part of the routine management of patients with gastroenteropancreatic neuroendocrine tumors. Somatostatin receptor scintigraphy (OctreoScan [ 111 In-pentetreotide]; Mallinckrodt, Inc.) detects these tumors with extremely high sensitivity and specificity (2). Moreover, recent results from clinical studies performing somatostatin receptor radionuclide therapy of these tumors are very promising (3,4).Prompted by the success of somatostatin receptor targeting, we have evaluated the overexpression of other peptide receptor families in tumors in vitro (1), with the aim, eventually, of being able to target in vivo a larger spectrum of tumors or individual tumors more efficiently with multiple pepti...