Design and Development of 99m Tc-‘4+1’-Labeled Dextran-Mannose Derivatives as Potential Radiopharmaceuticals for Sentinel Lymph Node Detection

Abstract

The synthesis, labeling, and biological evaluation of a dextran derivative (DCM-30-iso ) as potential radiopharmaceutical for sentinel lymph node imaging is presented. DCM-30-iso bears mannose as active moiety and isocyanide as ligand for technetium through the formation of a ‘4+1’ Tc(III) mixed-ligand complex. A second derivative without mannose (DC-25-iso) was also prepared and evaluated as control. DCM-30-iso and DC-25-iso were synthesized from dextran in four steps (>50% overall yield) and characterized by spectroscopic methods. Labeling with ^99mTc was achieved by reaction with 2,2′,2′′-nitrilotris(ethanethiol) and ^99mTc-EDTA. Radiochemical purity was above 90% and was stable for at least 4 hours postlabeling at 37°C. The identity of the ^99mTc complex was established through comparative HPLC studies using the well-characterized analogous Re-DC-25-iso complex. Biodistribution and imaging experiments of ^99mTc-DCM-30-iso showed high uptake in the popliteal lymph node, which could be blocked with preinjection of mannose, and very low uptake in other nodes and organs. The nonmannosylated ^99mTc-DC-25-iso derivative showed negligible uptake in all lymph nodes. The novel dextran-mannose derivative DCM-30-iso can be successfully labeled with ^99mTc to give a well-characterized ‘4+1’ complex with favorable biological properties as sentinel lymph node imaging agent.