Design, Synthesis, and Biological Evaluation of [18F]AlF-Labeled Integrin αvβ6-Targeting Tracers for Pancreatic Cancer Imaging

Xiaojun Zhang; Yong Huang; Fengping Gong; Keyin Chen; Yongqiang Zhang; Zhisheng Jie; Jiawen Huang; Ganghua Tang

doi:10.1021/acs.jmedchem.5c01189

Design, Synthesis, and Biological Evaluation of [¹⁸F]AlF-Labeled Integrin αvβ6-Targeting Tracers for Pancreatic Cancer Imaging

J Med Chem. 2025 Jun 28. doi: 10.1021/acs.jmedchem.5c01189. Online ahead of print.

Authors

Xiaojun Zhang¹, Yong Huang², Fengping Gong¹, Keyin Chen^{1

3}, Yongqiang Zhang⁴, Zhisheng Jie¹, Jiawen Huang¹, Ganghua Tang^{1

3}

Affiliations

¹ Key Laboratory Project of Guangdong Provincial Department of Education for Ordinary Universities and GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
² Department of Nuclear Medicine, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
³ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
⁴ Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong Province 510317, China.

PMID: 40580128
DOI: 10.1021/acs.jmedchem.5c01189

Abstract

Integrin αvβ6 is an attractive target for theranostic applications in pancreatic ductal adenocarcinoma (PDAC). Yet, there remains a lack of an ideal PET/CT tracer targeting αvβ6. In this study, we designed two novel PET/CT tracers [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L with hydrophilic linkers. Both [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L demonstrated favorable in vitro and in vivo properties, which are characterized by high hydrophilicity. In pancreatic tumor-bearing mice, micro-PET/CT imaging and biodistribution studies demonstrated that both [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L had favorable pharmacokinetic properties, good specific targeting to αvβ6, and tumor-to-background contrast. Between them, [¹⁸F]AlF-Asp2-αvβ6L demonstrated superior in vivo stability and accelerated renal clearance than [¹⁸F]AlF-Glc-αvβ6L, with comparable tumor uptake and retention and significantly lower kidney uptake. The results indicate that [¹⁸F]AlF-Asp2-αvβ6L is a promising PET/CT tracer for PDAC imaging.