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

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.

SUBMITTER: Hu K

PROVIDER: S-EPMC8756568 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Hu Kuan K Hu Kuan K Ma Xiaohui X Xie Lin L Zhang Yiding Y Hanyu Masayuki M Obata Honoka H Zhang Lulu L Nagatsu Kotaro K Suzuki Hisashi H Shi Rui R Wang Weizhi W Zhang Ming-Rong MR

ACS omega 20211222 1

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, [<sup>64</sup>Cu]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 [<sup>64</sup>Cu]CM-2, which exhibited specific bind ...[more]

PMID: 35036703

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Project description:BackgroundB cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE).MethodsFemale C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1-125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted.ResultsRadiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry-providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice.ConclusionCD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

Dataset Information

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

Publications

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

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