FGF19-Based Mini Probe Targeting FGFR4 for Diagnosis and Surgical Navigation of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a frequent malignancy
that has
a high death rate and a high rate of recurrence following surgery,
owing to insufficient surgical resection. Furthermore, HCC is prone
to peritoneal metastasis (HCC-PM), resulting in a significant number
of tiny cancer lesions, making surgical removal more challenging.
As a potential imaging target, FGFR4 is highly expressed in tumors,
especially in HCC, but is less expressed in the normal liver. In this
study, we used computational simulation approaches to develop peptide
I0 derived from FGF19, a particular ligand of FGFR4, and labeled it
with the NIRF dye, MPA, for HCC detection. In surgical navigation,
the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ
tumor and HCC-PM models, respectively, indicating considerable tumor
uptake. As a result, peptide I0 is an excellent clinical diagnostic
reagent for HCC, as well as a tool for surgically resecting HCC peritoneal
metastases.

肝细胞癌（Hepatocellular carcinoma, HCC）是一种高发恶性肿瘤，因手术切除不彻底，术后死亡率与复发率均居高不下。此外，肝细胞癌极易发生腹膜转移（HCC-PM），形成大量微小癌灶，进一步加剧了手术切除的难度。成纤维细胞生长因子受体4（FGFR4）作为潜在成像靶点，在肿瘤组织中呈高表达，尤以肝细胞癌为著，而在正常肝脏组织中表达水平较低。本研究通过计算模拟方法，开发出源自FGFR4特异性配体成纤维细胞生长因子19（FGF19）的肽I0，并采用近红外荧光（NIRF）染料MPA对其进行标记，用于肝细胞癌的检测。在手术导航场景中，肽I0在HepG2原位肿瘤模型与肝细胞癌腹膜转移模型中的肿瘤与背景比值（TBR）分别为9.31±1.36与8.57±1.15，表明其对肿瘤组织具有优异的摄取效果。综上，肽I0是一款性能卓越的肝细胞癌临床诊断试剂，同时也可作为肝细胞癌腹膜转移手术切除的辅助工具。