RT Journal Article
SR Electronic
T1 First-in-Humans Trial of Dasatinib-Derivative Tracer for Tumor Kinase-Targeted PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1580
OP 1587
DO 10.2967/jnumed.119.234864
VO 61
IS 11
A1 Simone Krebs
A1 Darren R. Veach
A1 Lukas M. Carter
A1 Milan Grkovski
A1 Monica Fornier
A1 Michael J. Mauro
A1 Martin H. Voss
A1 Daniel C. Danila
A1 Eva Burnazi
A1 Manda Null
A1 Kevin Staton
A1 Christina Pressl
A1 Bradley J. Beattie
A1 Pat Zanzonico
A1 Wolfgang A. Weber
A1 Serge K. Lyashchenko
A1 Jason S. Lewis
A1 Steven M. Larson
A1 Mark P.S. Dunphy
YR 2020
UL http://jnm.snmjournals.org/content/61/11/1580.abstract
AB We developed a first-of-kind dasatinib-derivative imaging agent, 18F-SKI-249380 (18F-SKI), and validated its use for noninvasive in vivo tyrosine kinase-targeted tumor detection in preclinical models. In this study, we assessed the feasibility of using 18F-SKI for PET imaging in patients with malignancies. Methods: Five patients with a prior diagnosis of breast cancer, renal cell cancer, or leukemia underwent whole-body PET/CT imaging 90 min after injection of 18F-SKI (mean, 241.24 ± 116.36 MBq) as part of a prospective study. In addition, patients underwent either a 30-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney (n = 2) or three 10-min whole-body PET/CT scans (n = 3) immediately after injection and blood-based radioactivity measurements to determine the time course of tracer distribution and facilitate radiation dose estimates. A subset of 3 patients had a delayed whole-body PET/CT scan at 180 min. Biodistribution, dosimetry, and tumor uptake were quantified. Absorbed doses were calculated using OLINDA/EXM 1.0. Results: No adverse events occurred after injection of 18F-SKI. In total, 27 tumor lesions were analyzed, with a median SUVpeak of 1.4 (range, 0.7–2.3) and tumor-to-blood ratios of 1.6 (range, 0.8–2.5) at 90 min after injection. The intratumoral drug concentrations calculated for 4 reference lesions ranged from 0.03 to 0.07 nM. In all reference lesions, constant tracer accumulation was observed between 30 and 90 min after injection. A blood radioassay indicated that radiotracer clearance from blood and plasma was initially rapid (blood half-time, 1.31 ± 0.81 min; plasma, 1.07 ± 0.66 min; n = 4), followed variably by either a prolonged terminal phase (blood half-time, 285 ± 148.49 min; plasma, 240 ± 84.85 min; n = 2) or a small rise to a plateau (n = 2). Like dasatinib, 18F-SKI underwent extensive metabolism after administration, as evidenced by metabolite analysis. Radioactivity was predominantly cleared via the hepatobiliary route. The highest absorbed dose estimates (mGy/MBq) in normal tissues were to the right colon (0.167 ± 0.04) and small intestine (0.153 ± 0.03). The effective dose was 0.0258 mSv/MBq (SD, 0.0034 mSv/MBq). Conclusion: 18F-SKI demonstrated significant tumor uptake, distinct image contrast despite low injected doses, and rapid clearance from blood.