What question did this study set out to answer?

This study aims to design an enhanced cyclic peptide for targeting TROP2 in cancer imaging.

April 5, 2026

Abstract 999: N/C-terminus modification: enhanced TROP2-targeting cyclic peptide for PET imaging

Key Points

This study aims to design an enhanced cyclic peptide for targeting TROP2 in cancer imaging.
Developed a chemically modified cyclic peptide targeting TROP2.
Synthesized using Fmoc-based solid-phase peptide synthesis and HBTU/collidine-mediated amide coupling.
Assembled stability and binding assays including CD spectroscopy and BLI.
Radiolabeled peptides with 68Ga and 64Cu for PET imaging validation.
Chemical modifications improved binding affinity and stability of cyclic peptides.
Demonstrated successful radiolabeling capacity indicating potential for clinical application.
Validated peptide interactions through various biochemical assays.

Abstract

Abstract Trophoblast cell surface antigen 2 (TROP2) has emerged as a compelling target in cancer therapy because it is highly overexpressed in many epithelial-derived malignancies while showing relatively low expression in normal tissues. To exploit this target, several modalities have been developed, including small molecules (e.g., Bruceine D) and antibody-based therapeutics (e.g., Sacituzumab govitecan). Despite these advances, challenges related to cost, specificity, and selectivity remain. In this flow, cyclic peptides have gained attention as attractive alternatives to conventional approaches due to their reduced conformational entropy and favorable biocompatibility.In this study, we report a chemically modified cyclic peptide designed for the visualization of TROP2 overexpression in cancer via PET/CT imaging. The peptide was modified at the N/C-terminus to promote π-π or cation-π interactions, thereby enhancing key biological properties such as binding affinity and stability. Each cyclic peptide was synthesized through Fmoc-based solid-phase peptide synthesis using HBTU/collidine-mediated amide coupling, and the final products were validated by mass spectrometry. The impact of the chemical modifications was assessed using circular dichroism (CD) spectroscopy, bio-layer interferometry (BLI), LogP analysis, and serum/glutathione stability assays. Radiolabeling with 68Ga and 64Cu demonstrated the preclinical capacity of this cyclic peptide. This strategy provides a versatile framework for the rational modification of cyclic peptides and supports the development of clinically relevant theragnostic agents. Citation Format: JONGMIN AN, Nisi Zhang, Marian Awadalla, SPENCER TUMBALE, Marina Raie, Basit Jan, Katherine W. Ferrara. N/C-terminus modification: enhanced TROP2-targeting cyclic peptide for PET imaging abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 999.

Ask AI

Helpful

Bookmark

View Full Paper