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.

Keywords: cell-based imaging; extracellular vesicle; leukocyte; magnetic resonance imaging; mesenchymal stromal cell; microorganisms; nanoparticle; near-infrared; nuclear imaging; platelets.

Figure 1

Distribution of cell types within a typical human colon tumor. Colors indicate respectively malignant epithelial cells (gray), immune cells (CD45, red), fibroblasts (fibroblast activation protein, blue), and endothelial cells (CD31, green), as stained in a multiplex analysis using a 40× field. Adapted from Sandberg et al. with permission [25].

Figure 2

Schematic overview of cell- and nanoparticle-based IGS tracers in a blood vessel near tumor tissue. Sizes of possible IGS tracers differ substantially. Logically, they rely on different mechanisms to reach their target tissue.