¹¹C-sorafenib and ¹⁵O-H₂O PET for early evaluation of sorafenib therapy

Abstract

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.