Preclinical evaluation of 68Ga-radiolabeled trimeric affibody for PDGFR β-targeting PET imaging of hepatocellular carcinoma

被引:5
作者
Cai, Huawei [1 ]
Li, Zhao [1 ]
Shi, Qiuxiao [2 ]
Yang, Hao [2 ,3 ,4 ]
Xiao, Liu [1 ]
Li, Mufeng [1 ]
Lin, Hua [1 ]
Wu, Xiaoai [1 ]
She, Tianshan [2 ]
Chen, Lihong [5 ]
Li, Lin [1 ]
Lu, Xiaofeng [2 ,3 ,4 ]
机构
[1] Sichuan Univ, West China Hosp, Dept Nucl Med & Lab Clin Nucl Med, Chengdu 610041, Peoples R China
[2] Sichuan Univ, West China Hosp, NHC Key Lab Transplant Engn & Immunol, Chengdu 610041, Peoples R China
[3] Sichuan Univ, West China Hosp, Inst Syst Genet, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610041, Peoples R China
[4] Sichuan Univ, West China Hosp, Sichuan Prov Engn Lab Pathol Clin Applicat, Chengdu 610041, Peoples R China
[5] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China
关键词
Hepatocellular carcinoma; PDGFR beta; Affibody; Ga-68; PET; BREAST-CANCER METASTASES; TUMOR ANGIOGENESIS; 1ST-LINE TREATMENT; EXPRESSION; C-11-CHOLINE; SORAFENIB; PERICYTES; DELIVERY; AFFINITY; CT;
D O I
10.1007/s00259-023-06260-x
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
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 (PDGFR beta). The aim of this study is to evaluate the feasibility of Ga-68-radiolabeled -Z(TRI) -([Ga-68]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 PDGFR beta as HCC biomarker. The trimeric affibody -Z(TRI) was conjugated with DOTA-NHS-ester and radiolabeled with Ga-68 to produce -[Ga-68]Ga-DOTA-ZTRI conjugate. Immunoreactivity and specific uptake of -[Ga-68]Ga-DOTAZTRI were assessed by dose-dependent cell binding, autoradiography, and biodistribution analysis. -[Ga-68]Ga-DOTA-ZTRI 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 -[Ga-68]Ga-DOTA-ZTRI in vivo. Results Excessive PDGFR beta was validated as a representative biomarker of HCC neovascularization. The radiolabeling of -[Ga-68]Ga-DOTA-Z(TRI) was achieved at more than 95% radiochemical yield. In vitro assays showed specific uptake of -[ Ga-68] Ga-DOTA-Z(TRI) in HCC tumor vessels by autoradiography. Animal PET/ CT imaging with -[Ga-68]Ga-DOTA-Z(TRI) successfully visualized the tumor lesions in primary HCC rats and rhesus monkey, and indicated radiation absorbed dose of 2.03E02 mSv/MBq for each scanning. Conclusions Our results demonstrated that -[68Ga]Ga-DOTA-ZTRI conjugate could be applied as a promising PET tracer for early diagnosis of hepatocellular carcinoma.
引用
收藏
页码:2952 / 2961
页数:10
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