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. <b>Methods:</b> 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 2 wk of sorafenib therapy. The main objective was to 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. <b>Results:</b>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 association with poorer prognosis and correlated with tumor perfusion (Spearman correlation coefficient = 0.671, <i>P</i> = 0.020). Interestingly, a decrease in tumor perfusion measured with ¹⁵O-H₂O PET after only 14 d 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. <b>Conclusion:</b> 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.