Development of a Stable Peptide-Based PET Tracer for Detecting CD133-Expressing Cancer Cells

Kuan Hu; Xiaohui Ma; Lin Xie; Yiding Zhang; Masayuki Hanyu; Honoka Obata; Lulu Zhang; Kotaro Nagatsu; Hisashi Suzuki; Rui Shi; Weizhi Wang; Ming-Rong Zhang

doi:10.1021/acsomega.1c04711

Development of a Stable Peptide-Based PET Tracer for Detecting CD133-Expressing Cancer Cells

ACS Omega. 2021 Dec 22;7(1):334-341. doi: 10.1021/acsomega.1c04711. eCollection 2022 Jan 11.

Authors

Affiliations

¹ Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan.
² Department of Vascular Surgery, General Hospital of People's Liberation Army, Beijing 100853, P. R. China.
³ Institute of Traumatology and Orthopaedics Beijing Jishuitan Hospital Beijing Laboratory of Biomedical Materials, Beijing 100035, P. R. China.
⁴ School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

Abstract

CD133 has been recognized as a prominent biomarker for cancer stem cells (CSCs), which promote tumor relapse and metastasis. Here, we developed a clinically relevant, stable, and peptide-based positron emission tomography (PET) tracer, [⁶⁴Cu]CM-2, for mapping CD133 protein in several kinds of cancers. Through the incorporation of a 6-aminohexanoic acid (Ahx) into the N terminus of a CM peptide, we constructed a stable peptide tracer [⁶⁴Cu]CM-2, which exhibited specific binding to CD133-positive CSCs in multiple preclinical tumor models. Both PET imaging and ex vivo biodistribution verified the superb performance of [⁶⁴Cu]CM-2. Furthermore, the matched physical and biological half-life of [⁶⁴Cu]CM-2 makes it a state-of-the-art PET tracer for CD133. Therefore, [⁶⁴Cu]CM-2 PET may not only enable the longitudinal tracking of CD133 dynamics in the cancer stem cell niche but also provide a powerful and noninvasive imaging tool to track down CSCs in refractory cancers.