Cancer remains one of the leading causes of death worldwide despite advances in diagnostic and treatment approaches. Current methods of detection and diagnosis remain inaccessible or expensive in nature; therefore, the development of non-invasive strategies towards early-stage cancer detection are important to allow for early intervention, treatment, and access. Liquid biopsies have emerged as a non-invasive source to improve routine cancer monitoring, however cancer biomarker abundance is low, leading to limitations in detection and accuracy. The recent discovery of neoplastic circulating hybrid cells (CHCs) in peripheral patient blood provide the potential to improve detection sensitivity of blood-based assays using novel molecular-targeting contrast agents specific to both circulating tumor cells (CTCs) and CHCs. Additionally, these contrast agents can be detected using diffuse in vivo flow cytometry (DiFC), enabling non-invasive enumeration of cancer cell burden. Herein, the development and validation of near infrared (NIR) molecularly-targeted contrast agents with specificity towards epithelial biomarkers expressed on CHC and CTCs is discussed.
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