Radiosynthesis and preclinical evaluation of 4-N-[¹⁸F]FDG-PBA as a novel PET tracer for tumor imaging

Abstract

Conventional [¹⁸F]FDG exhibits inherent drawbacks in liver tumor imaging, especially high physiological uptake in normal hepatic tissues, which severely compromises the diagnostic accuracy of hepatic tumors. To address these limitations, we synthesized a novel tracer, 4-N-[¹⁸F]FDG-PBA, via conjugation of [¹⁸F]FDG with 4-aminophenylboronic acid (PBA), aiming to improve the imaging performance of liver tumors. The total preparation time of 4-N-[¹⁸F]FDG-PBA was approximately 40 min, with a decay-uncorrected radiochemical yield of 10 ± 5% ( n  > 3) and a high radiochemical purity of over 95%. The tracer displayed outstanding stability in both in vitro and in vivo assays, with no observable defluorination phenomenon. Cellular uptake experiments in H22 hepatoma cells verified the rapid accumulation of the probe in tumor cells. Notably, treatment with the glucose transporter 1 (GLUT-1) inhibitor STF-31 exerted no significant inhibitory effect on tracer uptake (only 2.1% uptake reduction, p  = 0.13), demonstrating that 4-N-[¹⁸F]FDG-PBA relies on a unique transmembrane transport mechanism distinct from that of conventional [¹⁸F]FDG. Biodistribution analysis and micro-PET/CT imaging in tumor-bearing mouse models further confirmed that the tracer is primarily eliminated through the renal-urinary system. It presents low hepatic background signal, superior tumor visualization capability, and favorable tumor-to-background ratios for liver tumor imaging. The newly developed 4-N-[¹⁸F]FDG-PBA tracer possesses excellent stability, favorable pharmacokinetic characteristics, and a GLUT-independent tumor uptake mechanism. Collectively, these superior properties make it a promising novel radiotracer for high-precision liver tumor imaging.