Comparative biological evaluation of two [99mTc(CO)3]-dextran pyrazolyl mannose conjugates developed for use in sentinel lymph node detection.

ABSTRACT

AIM: This work aims to develop receptor based alternatives to the conventional colloidal tracers in sentinel lymph node (SLN) detection. In this study, we report the detailed biological evaluation of two dextran pyrazolyl mannose derivatives towards this purpose. METHODS: The dextran pyrazolyl mannose derivatives (DAPM4 and DAPM8) were labeled with the [99mTc(CO)3(H2O)3]+ core. In vitro saturation binding studies for the ligands were performed in mannose receptor-bearing RAW 264.7 macrophage precursor cells. Localization and pharmacokinetics studies of the tracers were conducted in normal Wistar rats with different ligand concentrations using in vivo activity distribution and scintigraphic imaging techniques. RESULTS: The ligands were labeled with the [99mTc(CO)3)]+ core in high yield and radiochemical purity (>90%). DAPM4 and DAPM8 showed specific uptake in RAW 264.7 cells. In vivo localization studies showed concentration-dependent uptake and selective retention of the [99mTc]-labeled complexes of DAPM4 and DAPM8 in the sentinel node with highly favorable values of popliteal extraction [PE] (%PEDAPM4=92.94%,%PEDAPM8=91.80% at 180 min p.i.) and rapid clearance from the site of injection when administered at 50 µg/mL ligand concentration. CONCLUSION: [99mTc(CO)3]-complexes of DAPM4 and DAPM8 show good in vivo potential to undergo further testing as agents for SLN detection in the clinic and their biological efficacy varies depending upon the concentration of ligands used for the procedure.