TY - JOUR T1 - <sup>11</sup>C-Sorafenib and <sup>15</sup>O-H<sub>2</sub>O PET for Early Evaluation of Sorafenib Therapy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 934 LP - 940 DO - 10.2967/jnumed.120.251611 VL - 62 IS - 7 AU - Lemonitsa H. Mammatas AU - Maqsood Yaqub AU - N. Harry Hendrikse AU - Otto S. Hoekstra AU - Richard J. Honeywell AU - Robert C. Schuit AU - Martijn Meijerink AU - Lothar A. Schwarte AU - Godefridus J. Peters AU - Henk M.W. Verheul AU - Adriaan A. Lammertsma AU - C. Willemien Menke-van der Houven van Oordt Y1 - 2021/07/01 UR - http://jnm.snmjournals.org/content/62/7/934.abstract N2 - 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 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. 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 association with poorer prognosis and correlated with tumor perfusion (Spearman correlation coefficient = 0.671, P = 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. 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. ER -