Preclinical evaluation of (68)Ga-radiolabeled trimeric affibody for PDGFRβ-targeting PET imaging of hepatocellular carcinoma

PURPOSE: Hepatocellular carcinoma (HCC) is a highly vascularized solid carcinoma and tumor vessel–targeted molecular imaging might be effective for early diagnosis of HCC. Herein, we developed a novel trimeric affibody (Z(TRI)) with highly specific binding to the platelet-derived growth factor receptor beta (PDGFRβ). The aim of this study is to evaluate the feasibility of (68)Ga-radiolabeled Z(TRI) ([(68)Ga]Ga-DOTA-Z(TRI)) as PET tracer for diagnosis of HCC. METHODS: The bioinformatics analysis of clinical database and immunoblotting of clinical specimens were performed to validate the potential of PDGFRβ as HCC biomarker. The trimeric affibody Z(TRI) was conjugated with DOTA-NHS-ester and radiolabeled with (68)Ga to produce [(68)Ga]Ga-DOTA-Z(TRI) conjugate. Immunoreactivity and specific uptake of [(68)Ga]Ga-DOTA-Z(TRI) were assessed by dose-dependent cell binding, autoradiography, and biodistribution analysis. [(68)Ga]Ga-DOTA-Z(TRI) PET/CT scanning of diethylnitrosamine (DEN)-induced primary HCC rats and a rare case of idiopathical HCC rhesus monkey was performed to evaluate the imaging capability and radiation dosimetry of [(68)Ga]Ga-DOTA-Z(TRI) in vivo. RESULTS: Excessive PDGFRβ was validated as a representative biomarker of HCC neovascularization. The radiolabeling of [(68)Ga]Ga-DOTA-Z(TRI) was achieved at more than 95% radiochemical yield. In vitro assays showed specific uptake of [(68)Ga]Ga-DOTA-Z(TRI) in HCC tumor vessels by autoradiography. Animal PET/CT imaging with [(68)Ga]Ga-DOTA-Z(TRI) successfully visualized the tumor lesions in primary HCC rats and rhesus monkey, and indicated radiation absorbed dose of 2.03E-02 mSv/MBq for each scanning. CONCLUSIONS: Our results demonstrated that [(68)Ga]Ga-DOTA-Z(TRI) conjugate could be applied as a promising PET tracer for early diagnosis of hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-023-06260-x.