Design and development of (99m)tc-'4+1'-labeled dextran-mannose derivatives as potential radiopharmaceuticals for sentinel lymph node detection.

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 (99m)Tc was achieved by reaction with 2,2',2''-nitrilotris(ethanethiol) and (99m)Tc-EDTA. Radiochemical purity was above 90% and was stable for at least 4 hours postlabeling at 37°C. The identity of the (99m)Tc complex was established through comparative HPLC studies using the well-characterized analogous Re-DC-25-iso complex. Biodistribution and imaging experiments of (99m)Tc-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 (99m)Tc-DC-25-iso derivative showed negligible uptake in all lymph nodes. The novel dextran-mannose derivative DCM-30-iso can be successfully labeled with (99m)Tc to give a well-characterized '4+1' complex with favorable biological properties as sentinel lymph node imaging agent.

Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core.

The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/µg.

Preparation and characterization of technetium and rhenium tricarbonyl complexes bearing the 4-nitrobenzyl moiety as potential bioreductive diagnostic radiopharmaceuticals. In vitro and in vivo studies.

The synthesis of a ligand containing a nitrobenzyl group as bioreductive pharmacophore and the preparation of the corresponding technetium and rhenium complexes are presented. (99m)Tc labelling was performed in high yield (>90%) by ligand substitution using fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) as precursor. The structure of the technetium complex was established by chromatographic comparison with the analogous rhenium compound which was fully characterized by elemental analysis, spectroscopic methods and X-ray crystallography. Reduction potential of the rhenium complex was in the characteristic range for bioreductive compounds. Biodistribution in normal mice was characterized by fast blood and soft tissue depuration and combined excretion via the hepatobiliary and urinary systems. Tumour uptake was low, probably due to low lipophilicity but tumour/muscle ratios were favourable as a consequence of high excretion.