PT  - JOURNAL ARTICLE
AU  - Simone Krebs
AU  - Darren R. Veach
AU  - Lukas M. Carter
AU  - Milan Grkovski
AU  - Monica Fornier
AU  - Michael J. Mauro
AU  - Martin H. Voss
AU  - Daniel C. Danila
AU  - Eva Burnazi
AU  - Manda Null
AU  - Kevin Staton
AU  - Christina Pressl
AU  - Bradley J. Beattie
AU  - Pat Zanzonico
AU  - Wolfgang A. Weber
AU  - Serge K. Lyashchenko
AU  - Jason S. Lewis
AU  - Steven M. Larson
AU  - Mark P.S. Dunphy
TI  - First-in-Humans Trial of Dasatinib-Derivative Tracer for Tumor Kinase-Targeted PET
AID  - 10.2967/jnumed.119.234864
DP  - 2020 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1580--1587
VI  - 61
IP  - 11
4099  - http://jnm.snmjournals.org/content/61/11/1580.short
4100  - http://jnm.snmjournals.org/content/61/11/1580.full
SO  - J Nucl Med2020 Nov 01; 61
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.