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Radiolabeled mannosylated dextran derivatives bearing an NIR-fluorophore for sentinel lymph node imaging

Tijdschriftbijdrage - Tijdschriftartikel

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.

Tijdschrift: Bioconjugate Chemistry
ISSN: 1043-1802
Issue: 11
Volume: 25
Pagina's: 1963-1970
Aantal pagina's: 8
Jaar van publicatie:2014
Trefwoorden:Animals, Dextrans, Female, Gallium Radioisotopes, Infrared Rays, Intraoperative Period, Isotope Labeling, Lymph Nodes, Mannose, Optical Imaging, Rats, Rats, Wistar, Biochemie & -fysica en Moleculaire biologie, Multidisciplinaire scheikunde , Organische en medische scheikunde