Cell-Based Tracers as Trojan Horses for Image-Guided Surgery

Abstract

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these ‘passive’ tracers, there are other, more ‘active’ approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, ‘humanized’ nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS.

Morphological Characteristics, Hemoglobin Content, and Membrane Mechanical Properties of Red Blood Cell Delivery Systems

“…Cell-based systems present a new type of platform in contemporary medicine for the delivery of a wide range of therapeutic, imaging, and biosensing cargos. − In particular, red blood cells (RBCs) are an attractive platform due to their potential biocompatibility, particularly if derived autologously, low immunogenicity, natural mechanisms for elimination, and innate ability for prolonged circulation. − For example, RBC delivery systems containing asparaginase have been investigated for the treatment of specific types of acute lymphoblastic leukemia, and in combination with chemotherapy, for the treatment of advanced pancreatic cancer in clinical trials. , …”

Phototheranostics Using Erythrocyte-Based Particles

“…A contemporary approach in engineering of delivery systems is based on the use of cells or cell-derived constructs to encapsulate the desired payload, or cell membranes to coat the payload. Examples include delivery systems based on macrophages, lymphocytes, neutrophils, and stems cells [2,3]. A fundamental principle underlying the use of cell-based or cell-derived systems is that the built-in mosaic of the cell membrane can provide the camouflaging machinery to protect the payload from recognition by immune cells and increase the bioavailability of the payload.…”

Endoglin/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review

“…Like for targeted PET, SPECT, and MRI, most targeted tracers for NIRF-based imaging consist of dyes conjugated to peptides, (derivatives of) monoclonal antibodies, aptamers consisting of single chain DNA/RNA, or of other carriers equipped with these tracing elements, such as nanoparticles, viruses, or cell-derived vesicles [ 88 ]. NIRF imaging further depends on a fluorescent dye and a near-infrared light source with a specific wavelength to illuminate the tissue of interest.…”