Noninvasively visualize the expression of LAPTM4B protein using a novel 18F-labeled peptide PET probe in hepatocellular carcinoma

Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. A PET targeting tracer named [18F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Radio-stability, cell uptake, micro PET/CT imaging and ex vivo biodistribution were performed for determining its stability, cell binding specificity, and tumor targeting in vivo. [18F]FP-LAP2H was successfully synthesized with radiochemical yields of 6–14% (decay-corrected yield) and molar activity of 10–44 GBq/μmol. The tracer showed stable (~90%) in phosphate-buffered saline, pH 7.4, and in human serum (~80%) for 2 h. In vitro cell uptake studies indicated the radioactivity accumulation in HCC cells was LAPTM4B protein-specific. Micro PET/CT demonstrated that implanted LAPTM4B positive HepG2 and BEL7402 tumors could be clearly visualized. The ex vivo biodistribution studies demonstrated that the tumor/liver ratio were 1.80 ± 0.65 and 2.09 ± 0.68 in implanted HepG2 and BEL7402 tumors respectively. Negative control and blocking experiments revealed that the radioactivity uptake in the HCC tumor was LAPTM4B protein-specific. [18F]FP-LAP2H appears to be a potential PET tracer for imaging LAPTM4B-positive HCC tumor. Further endeavors need to do to improve tumor/liver ratio. [Display omitted] •[18F]FP-LAP2H can be successfully radiosynthesis and feasible to detect LAPTM4B-positive Hepatocellular carcinoma•18F-FP-LAP2H showed excellent biochemical characteristics in vitro and in vivo•Micro PET/CT confirmed that LAPTM4B positive HepG2 tumor can be visualized clearly in vivo with a high tumor/muscle ratio•18F-FP-LAP2H has a potential to be a PET probe for detection of LAPTM4B-positive HCC