title: Radiolabeled mannosylated dextran derivatives bearing an NIR-fluorophore for sentinel lymph node imaging.
abstract: 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 ((99m)Tc or (68)Ga) and a near-infrared (NIR) reporter for pre- and/or intraoperative SLN mapping by nuclear and NIR 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-tetraacetic acid (DOTA) chelating units for labeling with fac-[(99m)Tc(CO)3](+) or (68)Ga(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.
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa , Estrada Nacional 10 (km 139,7), 2695-066 Bobadela LRS, Portugal.
authors.forename: Maurício
authors.initials: M
authors.lastname: Morais
authors.forename: Maria P C
authors.initials: MP
authors.lastname: Campello
authors.forename: Catarina
authors.initials: C
authors.lastname: Xavier
authors.forename: Johannes
authors.initials: J
authors.lastname: Heemskerk
authors.forename: João D G
authors.initials: JD
authors.lastname: Correia
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
authors.forename: Vicky
authors.initials: V
authors.lastname: Caveliers
authors.forename: Sophie
authors.initials: S
authors.lastname: Hernot
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
mesh_terms: D000818:Animals; D003911:Dextrans / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D005710:Gallium Radioisotopes; D007259:Infrared Rays; D007432:Intraoperative Period; D007553:Isotope Labeling; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000601:surgery; D008358:Mannose / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D011859:Radiography; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003911:Dextrans; D005710:Gallium Radioisotopes; D008358:Mannose