RT Journal Article SR Electronic T1 GPC-3 targeted hydrophilic peptides for PET imaging of hepatocellular carcinoma JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 934 OP 934 VO 58 IS supplement 1 A1 Wu, Hubing A1 Liu, Mei A1 Wang, Xiaohui A1 Sun, Muchuan A1 Conti, Peter A1 Chen, Kai YR 2017 UL http://jnm.snmjournals.org/content/58/supplement_1/934.abstract AB 934Objectives: Glypican-3 (GPC-3) is a cell surface protein which is overexpressed on the membrane of hepatocellular carcinoma (HCC) cells. Noninvasive imaging of GPC-3 expression in vivo is of particular interest for both GPC-3 targeted HCC diagnosis and treatment. In this study, we radiolabeled GPC-3 targeted peptides (GTPs) with 64Cu, and the resulting PET tracers were subsequently subject to biological evaluations in animal models. A highly hydrophilic linker was incorporated into the GTP sequence to construct L-GTP with an aim of reducing the tracer uptake in mouse liver.Methods: The immunofluorescence assay was used to identify the expression of GPC-3 and determine the binding of GTP in tumor cells. Both GTP and L-GTP were conjugated with NOTA chelator and radiolabeled with 64Cu in ammonium acetate buffer. The potency of the hydrophilic linker was investigated by comparing the biodistribution of 64Cu-NOTA-L-GTP vs. 64Cu-NOTA-GTP in normal mice. The HCC targeting efficacy of 64Cu-labeled GTPs was also studied by PET imaging in HepG2 tumor mouse model.Results: The immunofluorescence assay showed that GPC-3 is highly overexpressed on the membrane of HepG2 cells, and HepG2 cell uptake of L-GTP is strongly associated with the GPC-3 expression. 64Cu labeling was achieved in 85% decay-corrected yield with radiochemical purity of >98%. The specific activity of 64Cu-labeled GTPs was estimated to be ~40 MBq/nmol. 64Cu-NOTA-L-GTP demonstrated high hydrophilicity as determined by octanol-water partition coefficient measurements. PET imaging of 64Cu-NOTA-L-GTP at 1 h post intravenous injection in normal mice showed radioactivity was predominately accumulated in kidneys (8.74±1.31%ID/g) and bladder. Significantly lower liver uptake of 64Cu-NOTA-L-GTP (2.16±0.62%ID/g) was observed as compared to that of 64Cu-NOTA-GTP, suggesting that the hydrophilic linker greatly facilitates the tracer excretion via the renal system. PET study showed 64Cu-NOTA-L-GTP has preferential tumor uptake in HepG2 tumor xenografts with limited radioactivity uptake in mouse liver and intestine. The biodistribution results were consistent with the quantitative analysis of PET imaging.Conclusion: New 64Cu-labeled GTPs have been successfully developed for PET imaging of GPC-3 expression in HCC. The incorporation of a hydrophilic linker into the GTP significantly reduces the trace uptake in liver and improves the overall imaging efficacy of radiotracer in HCC. Convenient preparation, good GPC-3 specificity in mouse tumor xenografts, and favorable excretion profile of 64Cu-NOTA-L-GTP warrant further translational studies. Research Support: