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In situ radiotherapy with 111In-pentetreotide: initial observations and future directions
K E McCarthy1, E A Woltering, G D Espenan
1Department of Radiology, LSUMC Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans, USA.
Purpose:
Somatostatin and its analogues, such as octreotide and lanreotide, are used to treat neuroendocrine malignancies. Somatostatin analogues bind to somatostatin receptors (sst 1-5), which are differentially expressed in a wide variety of neoplasms. Following ligand receptor binding, a fraction of these complexes internalize. Internalization of radiolabeled somatostatin analogues, especially those that emit Auger electrons, may allow treatment of somatostatin-receptor-positive tumors by delivering a radioactive isotope to the cancer cell in a targeted fashion. 111In-pentetreotide, an sst-2-preferring somatostatin analogue, has been used for scintigraphic evaluation and management of neuroendocrine cancer patients. We hypothesized that binding and internalization of 111In-pentetreotide, an Auger electron emitter, may induce receptor-specific cytotoxicity and could be a useful therapeutic agent in somatostatin-receptor-expressing malignancies.
Methods:
To test this hypothesis, subjects who had failed conventional therapy and had somatostatin-receptor-positive malignancies, as determined by positive uptake on a 6.0 mCi 111In-pentetreotide scan, were treated with two monthly 180 mCi intravenous injections of 111In-pentetreotide. CT scans were obtained before therapy and within 30 days following the completion of the second 111In-pentetreotide dose. Toxicity was evaluated using standard criteria.
Results:
Fourteen patients were studied from February 1997 to August 1997. Clinical benefit occurred in six of 10 gastroenteropancreatic tumor patients. Objective partial radiographic responses occurred in two of 14 patients, and significant tumor necrosis (defined by changes in Hounsfield units) developed in six of the 10 gastroenteropancreatic tumor patients. Possible treatment-related toxicity included two patients experiencing grade 3/4 myelosuppression, and two patients had no measurable toxicity. The most common toxicity was grade 1/2 hemoglobin (N = 6).
Conclusion:
One hundred eighty millicurie (180-mCi) doses of 111In-pentetreotide are well tolerated and are an effective therapy in some subjects with somatostatin receptor-expressing tumors. The maximal tolerated dose of 111In-pentetreotide and the optimal dosing schedules remain to be determined.