RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP jnumed.120.251611
DO 10.2967/jnumed.120.251611
A1 Lemonitsa H. Mammatas
A1 Maqsood Yaqub
A1 N. Harry Hendrikse
A1 Otto S. Hoekstra
A1 Richard J. Honeywell
A1 Robert C. Schuit
A1 Martijn R. Meijerink
A1 Lothar A. Schwarte
A1 Godefridus J. Peters
A1 Henk M.W. Verheul
A1 Adriaan A. Lammertsma
A1 C. Willemien Menke-van der Houven van Oordt
YR 2020
UL http://jnm.snmjournals.org/content/early/2020/10/30/jnumed.120.251611.abstract
AB 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.