pharmacodynamic analysis of tumour perfusion assessed by 15o-water-pet imaging during treatment with sunitinib malate in patients with advanced malignancies药效学分析肿瘤灌注期间,15 o-water-pet成像评估治疗晚期恶性肿瘤患者的苹果酸舒尼替.pdfVIP

Scott et al. EJNMMI Research 2012, 2:31 /content/2/1/31 ORIGINAL RESEARCH Open Access Pharmacodynamic analysis of tumour perfusion assessed by 15O-water-PET imaging during treatment with sunitinib malate in patients with advanced malignancies 1* 1 1 1 2 1 Andrew M Scott , Paul L Mitchell , Graeme OKeefe , Timothy Saunder , Rodney J Hicks , Aurora Poon , 3 4 5 2 Charles Baum , Nicoletta Brega , Timothy J McCarthy and Guy C Toner Abstract Background: 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. Methods: 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. Results: 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 experienc