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 934
OP 940
DO 10.2967/jnumed.120.251611
VO 62
IS 7
A1 Mammatas, Lemonitsa H.
A1 Yaqub, Maqsood
A1 Hendrikse, N. Harry
A1 Hoekstra, Otto S.
A1 Honeywell, Richard J.
A1 Schuit, Robert C.
A1 Meijerink, Martijn
A1 Schwarte, Lothar A.
A1 Peters, Godefridus J.
A1 Verheul, Henk M.W.
A1 Lammertsma, Adriaan A.
A1 Menke-van der Houven van Oordt, C. Willemien
YR 2021
UL http://jnm.snmjournals.org/content/62/7/934.abstract
AB 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.