Preclinical evaluation of an ¹⁸F-trifluoroborate methionine derivative for glioma imaging

¹¹C–methionine (MET) is one of the most commonly used amino acid tracers for PET imaging of brain tumors. In this study, we report an ¹⁸F-labeled boron-derived methionine analogue, denoted as ¹⁸F-B-MET, as a potential substitute of ¹¹C–MET for glioma PET imaging.

¹⁹F-B-MET was synthesized from readily available chemicals according to our previous publication. For kit development, ¹⁹F-B-MET was aliquoted in quantities of 10 nmol for on-demand one-step labeling. The ¹⁸F-labeling was performed by ¹⁸F-¹⁹F isotope exchange, and quality control was performed by both HPLC and radio-TLC. Uptake of the tracer was determined in GL26, C6 and U87 tumor cells. PET imaging and the biodistribution assay were performed on mice bearing subcutaneous or orthotopic C6 and U87 tumor xenografts.

Starting with 740–1110 MBq ¹⁸F-fluoride, >370 MBq of ¹⁸F-B-MET was obtained in 25 min (n = 5) with >99% purity and high specific activity (>37 GBq/μmol). ¹⁸F-B-MET demonstrated excellent in vitro stability with <1% decomposition after incubation with plasma for 2 h. In vitro cell uptake assay showed that ¹⁸F-B-MET accumulated in tumor cells in a time dependent manner and could be competitively inhibited by natural methionine and other L-type transporter transported amino acids. In vivo biodistribution and imaging studies showed high tumor accumulation (2.99 ± 0.23 %ID/g, n = 6) compared with low uptake of brain (0.262 ± 0.05 %ID/g, n = 6) at 60 min after injection in a subcutaneous C6 tumor model. Orthotropic C6 and U87 tumors were clearly visualized with high tumor to brain ratios at 60 min post-injection, corroborating with tumor L-type amino acid transporter 1 (LAT-1) expression levels.

¹⁸F-B-MET was radiolabeled with high yield in a one-step labeling process, showed excellent pharmacokinetic properties in vivo, with high tumor-to-brain contrast.