11C-Sorafenib and 15O-H2O PET for Early Evaluation of Sorafenib Therapy

Abstract

Sorafenib leads to clinical benefit in a subgroup of patients,whereas 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 2wkof sorafenibtherapy. Themainobjectivewasto assess whether tumor 11C-sorafenib uptake predicts sorafenib concentrations during therapy in corresponding tumor biopsy samples measured with liquid chromatography tandem mass spectrometry. Secondary objectives included determining the association of 11C-sorafenib PET findings, perfusion 15O-H2O PET findings, and sorafenib concentrations after therapeutic dosing with response. Results: 11C-sorafenib PET findings did not predict sorafenib concentrations in tumor biopsy samples 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 an associationwith poorer prognosis and correlatedwith tumor perfusion (Spearman correlation coefficient 5 0.671, P = 0.020). Interestingly, a decrease in tumor perfusionmeasuredwith 15O-H2OPET after only 14 d of therapy showed an associationwith response,with a decrease in tumor perfusion of 56% 6 23% (mean 6 SD) versus 18%632%in patientswith 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.