McCarthy K E, Woltering E A, Espenan G D, Cronin M, Maloney T J, Anthony L B
Department of Radiology, LSUMC Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans, USA.
Cancer J Sci Am. 1998 Mar-Apr;4(2):94-102.
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.
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.
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).
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.
生长抑素及其类似物，如奥曲肽和兰瑞肽，用于治疗神经内分泌恶性肿瘤。生长抑素类似物与生长抑素受体（sst 1 - 5）结合，这些受体在多种肿瘤中差异表达。配体与受体结合后，一部分复合物会内化。放射性标记的生长抑素类似物的内化，尤其是那些发射俄歇电子的类似物，可能通过将放射性同位素靶向递送至癌细胞来治疗生长抑素受体阳性肿瘤。111In - 喷替肽，一种优先结合sst - 2的生长抑素类似物，已用于神经内分泌癌患者的闪烁显像评估和管理。我们推测，作为一种俄歇电子发射体的111In - 喷替肽的结合和内化可能诱导受体特异性细胞毒性，并且可能是治疗表达生长抑素受体的恶性肿瘤的一种有效治疗剂。
为了验证这一假设，对那些传统治疗失败且生长抑素受体阳性恶性肿瘤患者（通过6.0 mCi的111In - 喷替肽扫描阳性摄取确定）进行治疗，每月静脉注射两次180 mCi的111In - 喷替肽。在治疗前和第二次111In - 喷替肽剂量注射完成后30天内进行CT扫描。使用标准标准评估毒性。
1997年2月至1997年8月对14例患者进行了研究。10例胃肠胰肿瘤患者中有6例出现临床获益。14例患者中有2例出现客观的部分影像学缓解，10例胃肠胰肿瘤患者中有6例出现显著的肿瘤坏死（根据亨氏单位变化定义）。可能与治疗相关的毒性包括2例患者出现3/4级骨髓抑制，2例患者无可测量的毒性。最常见的毒性是1/2级血红蛋白降低（N = 6）。
180毫居里（180 - mCi）剂量的111In - 喷替肽耐受性良好，对一些表达生长抑素受体的肿瘤患者是一种有效的治疗方法。111In - 喷替肽的最大耐受剂量和最佳给药方案仍有待确定。
