A Conserved Molecular Signaling Target for Fluorescence Imaging of Solid Tumors

Abstract

HomeRadiology: Imaging CancerVol. 2, No. 3 PreviousNext Research HighlightsFree AccessA Conserved Molecular Signaling Target for Fluorescence Imaging of Solid TumorsGary D. LukerGary D. LukerGary D. LukerPublished Online:May 29 2020https://doi.org/10.1148/rycan.2020204014MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major Focus: To develop a peptide-based, near-infrared fluorescence imaging agent to detect abnormal signaling in tumors.■ Key Result: Discovered an octapeptide imaging agent that binds to a phosphorylated cell surface protein, Annexin A2.■ Impact: Sensitive detection of a wide range of solid tumors for image-guided surgery and targeted drug delivery.Molecular imaging agents and targeted therapies commonly rely on cell surface proteins selectively or preferentially overexpressed by malignant cells. The limited number of cancer-selective cell surface targets typically apply only to subtypes of one or a few cancers, necessitating repeated development and testing of new imaging agents. To overcome this challenge, Shen et al focused on imaging a protein modified by activation of a signaling process, phosphorylation, commonly dysregulated in most solid tumors. The investigators designed an octapeptide, near-infrared fluorescence imaging agent that bound with high affinity to the phosphorylated form of Annexin A2, a protein that localizes to the cell surface and drives invasion of cancer cells only when phosphorylated. The imaging agent bound to phosphorylated Annexin A2 in cancer cell lines, mouse models of cancer, and human cancer tissues from malignancies including breast cancer, pancreatic cancer, and soft-tissue sarcoma. Cancer cells also caused phosphorylation of Annexin A2 in adjacent fibroblasts and macrophages, allowing imaging of invasive margins of tumors. Normal fibroblasts and macrophages did not bind the imaging agent. In mouse models of breast cancer, the imaging probe detected lymph node metastases and tumor margins for highly effective image-guided surgery. When conjugated to the chemotherapy drug doxorubicin, the same octapeptide targeting agent also improved drug delivery to tumors while sparing dose-limiting toxicity to the heart. By targeting aberrant signaling in cancer, the investigators developed a new imaging agent with potentially broad applications for imaging and image-guided therapy of many solid tumors. The research team next plans to advance this imaging agent to clinical testing.Highlighted ArticleShen D, Xu B, Liang K, et al. Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2. Nat Biomed Eng 2020;4(3):298–313. doi: https://doi.org/10.1038/s41551-020-0528-7Highlighted ArticleShen D, Xu B, Liang K, et al. Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2. Nat Biomed Eng 2020;4(3):298–313. doi: https://doi.org/10.1038/s41551-020-0528-7 Crossref, Medline, Google ScholarArticle HistoryPublished online: May 29 2020 FiguresReferencesRelatedDetailsRecommended Articles Cancer Genomics and Important Oncologic Mutations: A Contemporary Guide for Body ImagersRadiology2017Volume: 283Issue: 2pp. 314-340Cryoablation and Immunotherapy for Breast Cancer: Overview and Rationale for Combined TherapyRadiology: Imaging Cancer2021Volume: 3Issue: 2High-Resolution Photoacoustic Tomography for Early-Stage Cancer Detection and Its Clinical TranslationRadiology: Imaging Cancer2020Volume: 2Issue: 3Breast Cancer Tissue Markers, Genomic Profiling, and Other Prognostic Factors: A Primer for RadiologistsRadioGraphics2018Volume: 38Issue: 7pp. 1902-1920Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical OpportunitiesRadiology: Imaging Cancer2021Volume: 3Issue: 3See More RSNA Education Exhibits Imaging Biomarkers in Targeted Therapies: From Quantitative Imaging to RadiomicsDigital Posters2019Breast Health in the Elderly: Implications for ImagingDigital Posters2020American Joint Committee on Cancer’s Staging System for Breast Cancer, Eighth Edition: Pictorial Guide for RadiologistsDigital Posters2020 RSNA Case Collection Locally Advanced Breast CancerRSNA Case Collection2021Male Breast CancerRSNA Case Collection2021Secondary Angiosarcoma of the BreastRSNA Case Collection2021 Vol. 2, No. 3 Metrics Downloaded 142 times Altmetric Score PDF download