Emerging biomedical imaging applications of tumor-derived extracellular vesicles for premetastatic niche detection: Biological rationale, engineering strategies, and translational challenges

Omkar Dhaygude1,2, Yun Chen1, Yamauchi Suguru2, Malcom Brock2, Franck Housseau3,4 and John Michel5 1 Department of Mechanical Engineering, School of Engineering, Johns Hopkins University, Baltimore, MD 21231, USA 2 Department of Surgery/Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA 3 Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA 4 University of Lille, Inserm, CHU Lille, CNRS, U1366-UMR9020 – CRCLille – Cancer Re-search Center of Lille, F-59000 Lille, France 5 Biomedical Engineering Program, Johns Hopkins University, Baltimore, MD 21231, USA Correspondence to: Franck Housseau, email:[email protected] John Michel, email:[email protected] Keywords: lung metastases; cancer imaging; theranostic; premetastatic niches; extra-cellular vesicles Received: August 07, 2025 Accepted: August 04, 2026 Published: August 28, 2026 Copyright: © 2026 Dhaygude et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Extracellular vesicles (EVs) are a heterogeneous population of membrane-enclosed nanoparticles naturally released by virtually all cell types, including exosomes, microvesicles, and other vesicular subtypes that differ in biogenesis, size, and molecular composition. By transporting proteins, lipids, nucleic acids, and metabolites, EVs mediate local and systemic intercellular communication and play a central role in tumor progression, organ-specific metastasis, and remodeling of distant microenvironments. Recent advances in EV isolation, engineering, and molecular profiling have accelerated interest in their use as nanomedicine platforms for both targeted delivery and cancer diagnostics. In particular, tumor-derived EVs (TEVs) exhibit intrinsic organotropism and participate in the establishment of premetastatic niches, making them promising vehicles for the targeted delivery of imaging probes to metastasis-prone tissues. This review discusses the emerging use of EVs as carriers of contrast and molecular imaging agents to enable visualization of premetastatic niches before overt metastatic lesions become detectable by conventional imaging modalities such as computed tomography. We highlight the biological rationale, engineering strategies, imaging applications, and translational challenges associated with EV-based probe delivery and consider how this approach may improve early detection of metastatic spread, risk stratification, and disease monitoring in oncology.