Integrin αvβ6–Targeted SPECT Imaging for Pancreatic Cancer Detection

Journal of Nuclear Medicine

Xianlei Sun¹  Zhaohui Zhu¹  Hongquan Zhang¹  Teng Ma¹  Jun Zhan¹  Yi Sun¹  Hao Liu¹  Jiyun Shi¹  Bing Jia¹  Fan Wang¹  Zhaofei Liu¹ 

关键词: pancreatic cancer;    molecular imaging;    integrin α_vβ₆;    phage display;    SPECT/CT;   

DOI  :  10.2967/jnumed.113.132969

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Integrin αvβ6, a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin αvβ6 is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a 99mTc-labeled integrin αvβ6–targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin αvβ6 expression. Methods: An integrin αvβ6–targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with 99mTc using tricine and TPPTS (trisodium triphenylphosphine-3,3′,3″-trisulfonate) as coligands. The in vitro and in vivo characteristics of 99mTc-HYNIC(tricine)(TPPTS)-HK (99mTc-HHK) were investigated in BxPC-3 (integrin αvβ6–positive) and HEK293 (integrin αvβ6–negative) models. The ability of 99mTc-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPECT/CT. Results: 99mTc-HHK showed high integrin αvβ6–binding specificity both in vitro and in vivo. 99mTc-HHK was cleared rapidly from the blood and normal organs except for the kidneys. The highest uptake (0.88 ± 0.12 percentage injected dose per gram) of 99mTc-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin αvβ6–positive tumors were obtained using 99mTc-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. Conclusion: 99mTc-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 expression in vivo. SPECT/CT with 99mTc-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin αvβ6–positive tumors.

【 授权许可】

Unknown