依维莫司降低神经内分泌肿瘤患者中 (89)Zr-贝伐珠单抗的肿瘤摄取。
Everolimus Reduces (89)Zr-Bevacizumab Tumor Uptake in Patients with Neuroendocrine Tumors.
机构信息
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
出版信息
J Nucl Med. 2014 Jul;55(7):1087-92. doi: 10.2967/jnumed.113.129056. Epub 2014 May 1.
UNLABELLED
Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients.
METHODS
Patients with advanced progressive well-differentiated NETs underwent (89)Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. (89)Zr-bevacizumab uptake was quantified by the maximum standardized uptake value (SUVmax). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly).
RESULTS
In 4 of the 14 patients entered, no tumor lesions were visualized with (89)Zr-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUVmax decreased during everolimus treatment, with a median of -7% at 2 wk (P = 0.09) and a median of -35% at 12 wk (P < 0.001). The difference in SUVmax at 2 and 12 wk with respect to SUVmax at baseline correlated with percentage change on CT at 6 mo (r(2) = 0.51, P < 0.05, and r(2) = 0.61, P < 0.01, respectively).
CONCLUSION
This study demonstrates variable (89)Zr-bevacizumab PET tumor uptake in NET patients. (89)Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial (89)Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGF-directed treatment in NET patients.
目的
依维莫司可提高晚期神经内分泌肿瘤（NET）患者的无进展生存期。目前，尚无生物标志物可用于早期选择将从依维莫司治疗中获益的患者。依维莫司可降低肿瘤细胞产生的血管内皮生长因子 A（VEGF-A）。因此，我们旨在研究依维莫司对 NET 患者放射性标记的 VEGF-A 抗体贝伐珠单抗的肿瘤摄取的影响。
方法
进展期高分化 NET 患者在依维莫司治疗前及治疗 2 周和 12 周时行（89）Zr-贝伐珠单抗 PET 扫描。采用最大标准化摄取值（SUVmax）定量（89）Zr-贝伐珠单抗摄取。根据实体瘤反应评估标准 1.1 （RECIST1.1），在 CT 上确定肿瘤反应和靶病灶直径总和的百分比变化。
结果
14 例患者中有 4 例（29%）用（89）Zr-贝伐珠单抗 PET 未检测到肿瘤病变。在其余患者中，CT 已知 1 cm 或更大的肿瘤病变的 19%可被检测到。依维莫司治疗期间肿瘤 SUVmax 下降，2 周时中位数为-7%（P=0.09），12 周时中位数为-35%（P<0.001）。与基线相比，2 周和 12 周时 SUVmax 的差异与 6 个月时 CT 的百分比变化相关（r2=0.51，P<0.05；r2=0.61，P<0.01）。
结论
本研究表明 NET 患者的（89）Zr-贝伐珠单抗 PET 肿瘤摄取存在差异。依维莫司治疗期间（89）Zr-贝伐珠单抗肿瘤摄取减少。（89）Zr-贝伐珠单抗 PET 可能成为 NET 患者抗 VEGF 靶向治疗的早期预测生物标志物。
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