Purpose: Sorafenib leads to clinical benefit in a subgroup of patients, while all are exposed to potential toxicity. Currently, no predictive biomarkers are available. The purpose of this study was to evaluate whether 11C-sorafenib and 15O-H2O PET have potential to predict treatment efficacy. Methods: In this prospective exploratory study, 8 patients with advanced solid malignancies and an indication for sorafenib treatment were included. Microdose 11C-sorafenib and perfusion 15O-H2O dynamic PET scans were performed before and after two weeks of sorafenib therapy. The main objective was to assess whether tumor 11C-sorafenib uptake predicts sorafenib concentrations during therapy in corresponding tumor biopsies measured with liquid chromatography tandem mass spectrometry (LC-MS/MS). Secondary objectives included the association of 11C-sorafenib PET, perfusion 15O-H2O PET and sorafenib concentrations after therapeutic dosing with response. Results:11C-sorafenib PET did not predict sorafenib concentrations in tumor biopsies during therapy. In addition, sorafenib plasma and tumor concentrations, were not associated with clinical outcome in this exploratory study. Higher 11C-sorafenib accumulation in tumors at baseline and day 14 of treatment showed association with poorer prognosis and was correlated with tumor perfusion (rs = 0.671, P = 0.020). Interestingly, a decrease in tumor perfusion measured with 15O-H2O PET after only 14 days of therapy showed an association with response, with a decrease in tumor perfusion of 56% ± 23% (mean ± SD) versus 18% ± 32% in patients with stable and progressive disease, respectively. Conclusion: Microdose 11C-sorafenib PET did not predict intratumoral sorafenib concentrations after therapeutic dosing, but the association between a decrease in tumor perfusion and clinical benefit warrants further investigation.
|Journal||Journal of nuclear medicine : official publication, Society of Nuclear Medicine|
|Publication status||E-pub ahead of print - 30 Oct 2020|