Radiolabeled Mannosylated Dextran Derivatives Bearing an NIR-Fluorophore for Sentinel Lymph Node Imaging

Current methods for sentinel lymph node (SLN) mapping involve the use of radioactivity detection with technetium-99m sulfur colloid and/or visually guided identification using a blue dye. To overcome the kinetic variations of two individual imaging agents through the lymphatic system, we report herein on two multifunctional macromolecules, 5a and 6a, that contain a radionuclide (Tc-99m or Ga-68) and a near-infrared (NW) reporter for pre- and/or intraoperative SLN mapping by nuclear and NW optical imaging techniques. Both bimodal probes are dextran-based polymers (10 kDa) functionalized with pyrazole-diamine (Pz) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) chelating units for labeling with fac-[Tc-99m(CO)(3)](+) or Ga-68(III), respectively, mannose units for receptor targeting, and NIR fluorophore units for optical imaging. The probes allowed a clear visualization of the popliteal node by single-photon emission computed tomography (SPECT/CT) or positron emission tomography (PET/CT), as well as real-time optically guided excision. Biodistribution studies confirmed that both macromolecules present a significant accumulation in the popliteal node (5a: 3.87 +/- 0.63% IA/organ; 6a: 1.04 +/- 0.26% IA/organ), with minimal spread to other organs. The multifunctional nanoplatforms display a popliteal extraction efficiency >90%, highlighting their potential to be further explored as dual imaging agents.