Enhancing the accumulation level of 3-[¹⁸F]fluoro-L-α-methyltyrosine in tumors by preloading probenecid

Introduction: 3-[¹⁸F]fluoro-α-methyl-L-tyrosine ([¹⁸F]FAMT) is a promising amino acid tracer targeting L-type amino acid transporter 1 (LAT1). One concern regarding the diagnosis using [¹⁸F]FAMT is the possibility of false-negative findings because of its relatively low accumulation level even in malignant tumors. Moreover, preloading probenecid, an organic anion transporter inhibitor, markedly increased the tumor accumulation level of radioiodine-labeled α-methyltyrosine. In this study, we evaluated the usefulness of preloading probenecid in improving the tumor-imaging capability of [¹⁸F]FAMT. Methods: Three biodistribution studies of [¹⁸F]FAMT were conducted in normal mice to elucidate the usefulness of probenecid preloading. Later, a biodistribution study and positron emission tomography (PET) imaging of [¹⁸F]FAMT were conducted with or without probenecid injection in tumor-bearing mice. Results: Probenecid preloading significantly delayed blood clearance and consequently enhanced the accumulation of [¹⁸F]FAMT in the pancreas, a LAT1-positive organ. The effects of probenecid preloading were independent of the administration route. Tumor accumulation level in the biodistribution study and the maximum standardized uptake value in tumors on PET imaging of the probenecid preloading group were significantly higher than those of the control (without probenecid injection) group in tumor-bearing mice. Conclusions: Preloading probenecid significantly delayed blood clearance and consequently enhanced the accumulation of [¹⁸F]FAMT in tumors. These results indicate that preloading probenecid could improve the diagnostic accuracy of [¹⁸F]FAMT.