Free somatostatin receptor fraction predicts the antiproliferative effect of octreotide in a neuroendocrine tumor model: implications for dose optimization.
Free somatostatin receptor fraction predicts the antiproliferative effect of octreotide in a neuroendocrine tumor model: implications for dose optimization.
复制标题
游离生长抑素受体分数预测了奥曲肽在神经内分泌肿瘤模型中的抗增生作用：对剂量优化的影响。
DOI：
10.1158/0008-5472.can-13-1199
复制
发表时间：
2013-12-01
期刊：
影响因子：
11.2
通讯作者：
Mahmood U
中科院分区：
文献类型：
--
作者：
Heidari P;Wehrenberg-Klee E;Habibollahi P;Yokell D;Kulke M;Mahmood U
生长抑素受体（SSTR）在分化良好的神经内分泌肿瘤（NET）中高度表达。奥曲肽是一种SSTR激动剂，已被用于抑制血管活性激素的产生并缓解功能性NET的激素分泌过多症状。在一项临床试验中，经验剂量的奥曲肽治疗延长了小肠神经内分泌（类癌）肿瘤患者的肿瘤进展时间，与症状状态无关。然而，还没有在患者群体中进行剂量优化研究，并且目前缺乏在个体基础上优化奥曲肽治疗剂量的方法。多种因素，如总肿瘤负荷、受体表达水平和非靶器官代谢/排泄，可能导致不同患者在给定剂量下SSTR奥曲肽占有率的变化。在这项研究中，我们报告了一种成像方法的发展，测量表面SSTR的表达和占用水平使用PET放射性示踪剂68镓DOTATOC。在动物模型中，用68 Ga-DOTATOC PET定量评估奥曲肽对SSTR的占用，发现占用增加导致肿瘤增殖率降低。结果表明，奥曲肽治疗期间的定量SSTR成像有可能确定NET中的受体占有率，从而使奥曲肽剂量在个体患者中易于优化。临床试验验证这种方法是必要的。
Somatostatin receptors (SSTRs) are highly expressed in well-differentiated neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to suppress the production of vasoactive hormones and relieve symptoms of hormone hypersecretion with functional NETs. In a clinical trial, an empiric dose of octreotide treatment prolonged time to tumor progression in patients with small bowel neuroendocrine (carcinoid) tumors, irrespective of symptom status. However, there has yet to be a dose optimization study across the patient population, and methods are lacking currently to optimize dosing of octreotide therapy on an individual basis. Multiple factors such as total tumor burden, receptor expression levels, and non-target organ metabolism/excretion may contribute to a variation in SSTR octreotide occupancy with a given dose among different patients. In this study, we report the development of an imaging method to measure surface SSTR expression and occupancy level using the PET radiotracer 68Ga-DOTATOC. In an animal model, SSTR occupancy by octreotide was assessed quantitatively with 68Ga-DOTATOC PET, with the finding that increased occupancy resulted in decreased tumor proliferation rate. The results suggested that quantitative SSTR imaging during octreotide therapy has the potential to determine the fractional receptor occupancy in NETs, thereby allowing octreotide dosing to be optimized readily in individual patients. Clinical trials validating this approach are warranted.