World J. Surg. 17, A.A.A. AA7 ' 1993 O WORLD Journal of SURGERY 9 1993 by the Soci›233 Internationale de Chirurgie Use of Isotope-Labeled Somatostatin Analogs for Visualization of Islet Cell Tumors C.H.J. van Eyck, H.A. Bruining, J.-C. Reubi, W.H. Bakker, H.Y. Oei, E.P. Krenning, and S.W.J. Lamberts Departments of Medicine, Surgery, and Nuclear Medicine, Erasmus University, Rotterdam, The Netherlands The results of visualization of the islet cell tumors of 25 patients after intravenous administration of two isotope-labeled somatostatin analogs (123I-Tyr3-octreotide and 111In-octreotide) are described. The prirnary tumors, as weil as previously often unrecognized distant metastases were visualized in 20 of the 25 patients (80%). Parallel in vitro detection of somatostatin receptors on those tumors that had also been visualized in vivo indicates that the ligand binding to the tumor in vivo indeed represents binding to specific somatostatin receptors. The detection of somatostatin receptors on these tumors in vivo predicted a good suppres- sive effect of octreotide on hormonal hypersecretion by these tumors. It is an easy, quick, harmless procedure that is valuable for Iocalization of primary endocrine pancreatic tumors and their often radiologically and clinically not yet recognized metastases. Somatostatin receptors have been shown to be present on a variety of tumors that arise in tissues also containing these receptors in the normal state. Large numbers of high-aflinity somatostatin receptors have been found on most growth hor- mone-secreting pituitary adenomas as weU as on most meta- static islet cell tumors and carcinoids [1-3]. In parallel, chronic therapy with octreotide normalizes clinical symptomatology and the biochemical abnormalities in most acromegalic pa- tients: both the hypersecretion of growth hormone, and the elevated circulating levels of insulin-like growth factor I (virtu- ally) normalize in most instances [4]. Hormonal hypersecretion from (metastatic) endocrine pancreati c tumors and carcinoids is also well controlled during octreotide treatment in most pa- tients, and clinical symptomatology greatly improves. Interest- ingly, evidence for control of tumor growth during somatostatin analog treatment has been observed in some of these patients [5]. These results led to an instant improvement in the quality of life of the patients, making the clinical introduction of oc- treotide a major breakthrough in the treatment of these endo- crine cancers. Study Rationale It was remarkable to us that in the in vitro autoradiographic studies of most of these endocrine tumors (pancreatic and Offprint requests: S.W.J. Lamberts, Department of Medicine, Uni- versity Hospital Dijkzigt, 40 Dr. Molewaterplein, 3015 GD Rotterdam, The Netherlands. carcinoids) there was virtually always a high density of soma- tostatin receptors present within these tumors, contrasting sharply with the virtual absence of visible binding sites in the surrounding "normal" tissue, which was known also to contain these receptors (Fig. 1) [1-3]. The presence of higher numbers or a higher affinity of the somatostatin receptors in many of these tumors seemed also reflected by the clinical observation that tumorous hormone secretion (i.e., in acromegalic or gas- trinoma patients) was suppressed much longer after the single subcutaneous administration of octreotide than was normal growth hormone and gastrin secretion in healthy individuals [6]. Study Protocol and Results These considerations led us to explore whether it was possible to detect somatostatin receptor-positive tumors in vivo after the administration of a radioactive iodine-labeled analog [7]. In a way, one might call this approach "in vivo autoradiography" of somatostatin receptor-p0sitive tumors. Tyr3-octreotide is a somatostatin analog with tyrosine in position 3, whereas phe- nylalanine is present at that place in octreotide. The biologic activities of octreotide and Tyr3-octreotide are similar. We coupled Tyr3-octreotide to 123I and injected 37-555 MBq 1231- Tyr3-octreotide intravenously into patients suspected to have somatostatin receptor-positive tumors, and planar or emission computed tomographic (ECT) images were obtained with a gamma camera. After the bolus injection of radioiodinated Tyr3-octreotide, rapid accumulation of radioactivity was seen in the liver. About 50% of the activity was cleared from the blood pool within 2 minutes after injection:, and localization of a variety of tumors and their metastases was possible. The 123I-Tyr3-octreotide scanning procedure revealed local- ization of the primary tumor, its previously unknown metasta- ses, or both in 7 of 9 patients with islet cell tumors. In 5 of the 7 positive tumors, we subsequently examined the surgically removed tumor [8]. There was a close relation between the in vitro detection of somatostatin receptors in these tumors using autoradiography and the gamma camera pictures obtained after injection of 123I-Tyr3-octreotide. This finding indicates that the ligand binding to the tumor in vivo represents binding to specific