Search

Lingzhou Zhao,* Jiali Gong,* Qinli Qi,* Changcun Liu, Hongxing Su, Yan Xing, Jinhua Zhao Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinhua Zhao; Yan Xing, Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 21 3779 8352, Email zhaojinhua1963@126.com; xy.1@163.comPurpose: The unique structure of nanobodies is advantageous for the development of radiopharmaceuticals for nuclear medicine. Nanobodies targeted to human epidermal growth factor receptor 2 (HER2) can be used as tools for the imaging and therapy of HER2-overexpressing tumors. In this study, we aimed to describe the generation of a 131I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer.Methods: The anti-HER2 nanobody NM-02 was labeled with 131I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group.Results: 131I-NM-02 could be readily prepared with satisfactory radiochemical purity and stability in vitro. Apparent tumor uptake was observed in HER2-positive tumor-bearing mice with rapid blood clearance and favorable biodistribution. 131I-NM-02 could significantly inhibit tumor growth and extend the life of these mice with good organ compatibility. Negligible tumor accumulation and inhibitory effects of 131I-NM-02 were observed in the negative control group.Conclusion: 131I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.Keywords: human epidermal growth factor receptor 2, nanobody, 131I, targeted radionuclide therapy

OBJECTIVE Type IV collagen (Col-IV) is a prospective biomarker for diagnosing and treating of unstable thoracic aortic aneurysm and dissection (TAAD). This study aims to evaluate the feasibility of 68Ga-labeled WVP peptide (68Ga-DOTA-WVP) as a novel Col-IV-targeted probe for TAAD biological diagnosis using PET/CT. METHODS WVP peptide was modified with bifunctional chelator DOTA for 68Ga radiolabeling. Immunohistochemical staining was used to evaluate the expression and location of Col-IV and elastin in aortas treated with 3-aminopropionitrile fumarate (BAPN) at different time points (0, 2, and 4 weeks). The imaging performance of 68Ga-DOTA-WVP was investigated using Micro-PET/CT in a BAPN-induced TAAD mouse model. The relationship between 68Ga-DOTA-WVP uptake in aortic lesions and the serum levels of TAAD-related biomarkers including D-dimer, C-reactive protein (CRP), and serum soluble suppression of tumorigenicity-2 (sST2) was also analyzed. RESULTS 68Ga-DOTA-WVP was readily prepared with high radiochemical purity and stability in vitro. 68Ga-DOTA-WVP Micro-PET/CT could detect Col-IV exposure of unstable aneurysms and early dissection in BAPN-induced TAAD mice, but little 68Ga-DOTA-WVP uptake was shown in the control group at each imaging time point. The differences of Col-IV expression and distribution of 68Ga-DOTA-WVP both in TAAD and control groups further verified the imaging efficiency of 68Ga-DOTA-WVP PET/CT. Additionally, a higher sST2 level was found in the imaging positive (n = 14) than the negative (n = 8) group (9.60 ± 1.14 vs. 8.44 ± 0.52, P = 0.014). CONCLUSION 68Ga-DOTA-WVP could trace the exposure and abnormal deposition of Col-IV in enlarged and early injured aortas, showing a potential for biological diagnosis, whole-body screening, and progression monitoring of TAAD.