Intraoperative use of gamma-detecting probes to localize neuroendocrine tumors

Neuroendocrine tumors are characterized by the expression of different peptides and biogenic amines. These rare tumors tend to grow slowly and are notoriously difficult to localize, at least in the early stages. Surgical removal is the only definitive therapeutic option for neuroendocrine tumors and relief from hyperfunctional status. The effectiveness of surgical treatment is invariably dependent upon the complete surgical excision of all tumor tissue, because microscopic and occult disease not readily seen by the surgeon may remain in situ, leading to shortened survival. Therefore, pre- and intraoperative localization of the primary as well as of metastatic tumors is of utmost importance. Radioguided surgery (RGS) is an intraoperative technique that enables the surgeon to localize radiolabelled tissue based on the characteristics of the various tissues. Concerning gastroenteropancreatic tumors (GEP), intraoperative gamma probe examination is able to reveal small tumor sites accumulating (111In-DTPA-D-Phe1)-pentetreotide more efficiently (> 90%) than somatostatin receptor scintigraphy (68%-77%), because lesions with a size smaller than 5 mm in greatest dimension could be identified. Furthermore, RGS identified 57% more lesions when compared to the "palpating finger" of the surgeon. In medullary thyroid cancer (MTC), surgical removal of the tumor is the first and most efficient treatment of the disease. Persistent or increasing serum calcitonin and carcinoembryonic antigen (CEA) levels imply tumor recurrence after thyroid ablation. For imaging recurrent MTC many radiopharmaceuticals have been used to visualize tumor sites, but none of them has shown excellent sensitivity. Preoperative somatostatin receptor scintigraphy and intraoperative RGS in patients with recurrent MTC demonstrate only part of the tumor sites and cannot visualize small tumor sites (less than 10 mm). In comparison, RGS using 99mTc(V)-DMSA detects metastases with a size of 5 mm in diameter, whereas the "palpating finger" of the surgeon localized metastases with a size of more than 1 cm in diameter. In patients with recurrent MTC, intraoperative gamma probe examination is able to localize over 30% more tumor lesions when compared with conventional preoperative imaging modalities and surgical findings. MIBG scintigraphy is the most sensitive technique for the detection and staging of neuroblastoma (sensitivity 92%; specificity nearly 100%). Intraoperative RGS with iodine labelled MIBG has been developed to improve the definition of tumor limits or to localize small, nonpalpable tumors. Comparison of 123I- and 125I-labelled MIBG revealed a sensitivity of 91% and 92%, respectively; the specificity of 125I (85%) was significantly higher than that of 123I (55%). In addition to scintigraphy of the adrenal glands by precusors of adrenal hormones, imaging with a radiolabelled somatostatin analogue is possible; however, (111In-DTPA-D-Phe1)-pentetreotide is not specific for any adrenal disease or function and the relatively high radioligand accumulation in the kidneys limited the use for detection of tumors in the area of the adrenal glands.