Home Products Cited in Publications Worldwide Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase
ACS Pharmacol. Transl. Sci.,2023,6(3):410-421.
Li, Kaixuan; Wang, Mingqian; Akoglu, Melike; Pollard, Alyssa C.; Klecker, John B.; Alfonso, Patricia; Corrionero, Ana; Prendiville, Niall; Qu, Wenchao; Parker, Matthew F. L.; Turkman, Nashaat; Cohen, Jules A.; Tonge, Peter J.
DOI:10.1021/acsptsci.2c00215 PMID:36926452
Bruton′s tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases. To aid in the discovery and development of BTK inhibitors and improve clin. diagnoses, we have developed a positron emission tomog. (PET) radiotracer based on a selective BTK inhibitor, remibrutinib. [18F]PTBTK3 is an aromatic, 18F-labeled tracer that was synthesized in 3 steps with a 14.8 ± 2.4% decay-corrected radiochem. yield and ≥99% radiochem. purity. The cellular uptake of [18F]PTBTK3 was blocked up to 97% in JeKo-1 cells using remibrutinib or non-radioactive PTBTK3. [18F]PTBTK3 exhibited renal and hepatobiliary clearance in NOD SCID (non-obese diabetic/ severe combined immunodeficiency) mice, and the tumor uptake of [18F]PTBTK3 in BTK-pos. JeKo-1 xenografts (1.23 ± 0.30% ID/cc) was significantly greater at 60 min post injection compared to the tumor uptake in BTK-neg. U87MG xenografts (0.41 ± 0.11% ID/cc). In the JeKo-1 xenografts, tumor uptake was blocked up to 62% by remibrutinib, indicating the BTK-dependent uptake of [18F]PTBTK3 in tumors.
PET imaging ; BTK ; tumor ; fluorine-18 ; Jeko-1 ; U87MG