2. Academic Validation
  3. Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase

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 Feb 10;6(3):410-421. doi: 10.1021/acsptsci.2c00215.
Kaixuan Li 1 1,  Mingqian Wang 1 1,  Melike Akoglu 1 1,  Alyssa C Pollard 1 1,  John B Klecker 1 1,  Patricia Alfonso 2,  Ana Corrionero 2,  Niall Prendiville 2,  Wenchao Qu 3 3 1,  Matthew F L Parker 3 1,  Nashaat Turkman 3 3,  Jules A Cohen 3 3,  Peter J Tonge 1 3 1 3
Affiliations

Affiliations

  • 1 Center for Advanced Study of Drug Action and Department of Chemistry, Stony Brook University, John S. Toll Drive, Stony Brook, New York 11794-3400, United States.
  • 2 Enzymlogic S.L., QUBE Technology Park, C/Santiago Grisolía, 2, 28760 Madrid, Spain.
  • 3 Department of Psychiatry, Department of Radiology, Department of Medicine, Stony Brook Cancer Center, and Facility of Experimental Radiopharmaceutical Manufacturing (FERM), Stony Brook Renaissance School of Medicine, Stony Brook University, Stony Brook, New York 11794, United States.
PMID: 36926452 DOI: 10.1021/acsptsci.2c00215
Abstract

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 clinical diagnoses, we have developed a positron emission tomography (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 radiochemical yield and ≥99% radiochemical 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-positive JeKo-1 xenografts (1.23 ± 0.30% ID/cc) was significantly greater at 60 min post injection compared to the tumor uptake in BTK-negative 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.

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