[18F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors

Zhenfeng Liu; Guanghua Wen; Yuqiao Huang; Yanzhao Dong; Zewei Wang; Ahmad Alhaskawi; Shuyi Zhang; GuoLin Wang; Qianni Ye; Haiying Zhou; Hui Lu; Mengjie Dong

doi:10.3389/fonc.2023.1126721

[¹⁸F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors

Front Oncol. 2023 May 22:13:1126721. doi: 10.3389/fonc.2023.1126721. eCollection 2023.

Authors

Zhenfeng Liu¹, Guanghua Wen², Yuqiao Huang³, Yanzhao Dong³, Zewei Wang⁴, Ahmad Alhaskawi⁵, Shuyi Zhang¹, GuoLin Wang¹, Qianni Ye¹, Haiying Zhou⁵, Hui Lu⁵, Mengjie Dong^{1

6}

Affiliations

¹ Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Department of Nuclear Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China.
³ Institute of Translational Medicine, Zhejiang University, Hangzhou, China.
⁴ Department of Clinical Medicine, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Department of Orthopedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁶ Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, China.

Abstract

Background: The cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.

Methods: In this study, [¹⁸F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.

Results: Radiolabeling of ADH-1 with [¹⁸F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of >97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [¹⁸F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.

Conclusion: [¹⁸F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [¹⁸F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors.

Keywords: EMT; N-cadherin; PET imaging probe; [18 F]AlF-NOTA-ADH-1; cancer.

Grants and funding

This project was supported by the National Natural Science Foundation of China (Grant No. 81771884), Zhejiang Natural Science Foundation (LTGY23H180014) and Shenzhen Municipal Natural Science Foundation (JCYJ20220530160213030). The funding body only provided financial support, and the design of the study, analysis, and interpretation of data and the article writing were independently completed by the authors of this article.