Centre for PET, Ludwig Institute for Cancer Research and Ludwig Oncology Unit, Austin Hospital, Studley Road, Heidelberg, Victoria, 3084, Australia.
EJNMMI Res. 2012 Jun 9;2(1):31. doi: 10.1186/2191-219X-2-31.
We evaluated pharmacodynamic changes in tumour perfusion using positron emission tomography (PET) imaging with 15O-water to assess biological response to sunitinib, a multitargeted tyrosine kinase inhibitor.
Patients with advanced malignancies received sunitinib 50 mg/day orally, once daily for 4 weeks on treatment, followed by 2 weeks off treatment, in repeated 6-week cycles. Quantitative measurement of tumour perfusion was assessed using 15O-water-PET at baseline and after 2 weeks of treatment. At least one reference tumour lesion was included in the fields of view and assessed at both time points. Patients also underwent 18 F-fluorodeoxyglucose (FDG)-PET imaging at baseline and after 2 and 4 weeks of treatment. Radiological response of the reference tumour lesion and overall radiological response were assessed at week 12. Serum pharmacokinetic and biomarker analyses were also performed.
Data were available for seven patients. Compared with baseline, all patients experienced a decrease in reference tumour blood flow ranging from 20 % to 85 % and also a reduction in the FDG standard uptake value ranging from 29 % to 67 %. Six patients experienced a partial metabolic response based on FDG-PET criteria. Four patients had stable disease defined by radiological response (Response Evaluation Criteria in Solid Tumors) lasting between 4 and 12 cycles. An association between perfusion change and clinical benefit, and biomarker levels including vascular endothelial growth factor was observed.
Administering sunitinib to patients with advanced malignancies is associated with early biological responses, including decreased blood flow in secondary tumour deposits.
我们使用 15O-水正电子发射断层扫描（PET）成像评估肿瘤灌注的药效学变化，以评估舒尼替尼（一种多靶点酪氨酸激酶抑制剂）对生物反应。
晚期恶性肿瘤患者接受舒尼替尼 50mg/天，口服，治疗 4 周，每天一次，然后停药 2 周，重复 6 周周期。在基线和治疗 2 周后使用 15O-水-PET 评估肿瘤灌注的定量测量。在这两个时间点，至少有一个参考肿瘤病变被包括在视野内并进行评估。患者还在基线、治疗 2 周和 4 周后进行 18F-氟脱氧葡萄糖（FDG）-PET 成像。在第 12 周评估参考肿瘤病变的放射学反应和整体放射学反应。还进行了血清药代动力学和生物标志物分析。
有 7 名患者的数据可用。与基线相比，所有患者的参考肿瘤血流均减少了 20%至 85%，FDG 标准摄取值也减少了 29%至 67%。根据 FDG-PET 标准，6 名患者出现部分代谢反应。4 名患者的疾病稳定（实体瘤反应评价标准），持续 4 至 12 个周期。观察到灌注变化与临床获益以及包括血管内皮生长因子在内的生物标志物水平之间存在关联。
向晚期恶性肿瘤患者给予舒尼替尼与早期生物学反应相关，包括继发性肿瘤沉积的血流减少。
