Somatostatin receptor imaging and therapy: An ever expanding choice

Full text: Cells express a variety of different receptor proteins on their surface, some of which have a high affinity for regulatory peptides, such as somatostatin. Somatostatin receptors (SSTR) are over-expressed in several human tumours, especially those of neuroendocrine origin. The biological effects of SSTR are mediated by five specific receptor subtypes (SSTR 1-5) to which the native peptide binds. However, somatostatin analogues have major differences in their affinities for different receptor subtypes. DTPA-octreotide binds with reasonably high affinity to SSTR 2 and with low affinity to SSTR 5. RC-160 has enhanced binding affinity to SSTR 4, while depreotide preferentially binds to SSTR 2, 3 and 5. DOTA-lanreotide binds to SSTR 2, 3, 4 and 5 with high affinity, and to SSTR 1 with low affinity. DOTA-Tyr3-octreotate exhibits the highest affinity for SSTR 2. Somatostatin analogues labelled with a variety of gamma-, positron- and beta-emitters, are becoming of increasing interest in tumour targeting for either the localization or the targeted radiotherapy of neoplasms. The aim of this study was to evaluate the use of 99mTc-depreotide in visualisation of neuroendocrine tumours and other tumours expressing somatostatin receptors, when 111In-pentetreotide and/or 123I-MIBG scans were negative or inconclusive and to choose a suitable radiopharmaceutical for targeted therapy. The case records of 23 patients (17 women and 6 men, mean age 56.78 range 26-78) who underwent 99mTc-depreotide scans over the period from January 2004 to March 2005 were reviewed. Fourteen patients presented with neuroendocrine tumours, 2 with Merkel cell tumours, 2 with thymic carcinomas, 3 with medullary and 1 with papillary carcinoma of the thyroid. Two patients had previous 90Y-DOTA-lanreotide, one 131I-MIBG and one 153Sm-EDTMP therapy. Whole body imaging was performed with tomography of the liver at 1 and 4 hours after intravenous injection of 700-750 MBq of 99mTc-depreotide. 21/23 patients had 111Inpentetreotide whole-body scintigraphy with tomography of the upper abdomen. Twelve of these patients also had 123I-MIBG imaging. 2/23 had 18F-FDG-PET scans which were negative. One experienced reader reviewed all the scans and compared uptake between the tracers. Results showed that 99mTc-depreotide imaging demonstrated positive findings in 19 cases (82.6%) and was superior to 111Inpentetreotide imaging in 15 cases and PET in 2 cases. In 2 cases 111In-pentetreotide was better than 99mTc-depreotide. 123I-MIBG scintigraphy was positive only in two cases. All three imaging modalities were negative in 2 cases. One patient had two populations of tumour cells, presenting with different pattern of uptake on depreotide, pentetreotide and MIBG scan. According to the intensity of uptake different possible treatments were recommended: in 5 cases 90Y-DOTA-lanreotide, in 1 case 131I-MIBG and in 1 case intra-arterial treatment with 90Y-sirspheres for wide spread liver metastases. We conclude that 99mTc-depreotide scintigraphy is a very promising method in the visualisation of somatostatin receptor expressing tumours and in patient selection for the targeted therapy, choice of therapy and method of administration. (author)