99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification

Tc-99m-labeled mannosyl-neoglycoalbumin (NMA) was prepared and evaluated as a radiopharmaceutical for sentinel lymph node (SLN) identification, since Tc-99m-labeled human serum albumin (HSA) rapidly cleared from injection sites. NMA was conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and reacted with [Tc-99m](tricine)(2) to prepare [Tc-99m](HYNIC-NMA)(tricine)(2). After subcutaneous injection of [Tc-99m](HYNIC-NMA)(tricine)(2) from murine foot pad, radioactivity levels in the popliteal and lumbar lymph nodes, the injection site and other tissues were compared with those of [Tc-99m](HYNIC-HSA)(tricine)(2) and Tc-99m-labeled colloidal rhenium sulfate ([Tc-99m]colloid). [(TC)-T-99m](HYNIC-NMA)(tricine)2 demonstrated significantly higher radioactivity levels in the popliteal lymph node, the SLN in this model, than did [Tc-99m](HYNIC-HSA)(tricine)(2) and [Tc-99m]colloid at 0.5, 1, and 6 h post-injection. [Tc-99m](HYNIC-NMA)(tricine)(2) showed a dose-dependent decrease in the popliteal accumulation while the radioactivity levels in the blood, liver and spleen increased with an increase in the molar dose of NMA. [Tc-99m]colloid registered a decrease in the radioactivity levels in the popliteal lymph node, blood, liver, and spleen with dilution. However, the radioactivity levels at the injection site increased with dilution of [ Tc-99m] colloid. Both [Tc-99m](HYNIC-NMA)(tricine)(2) and [Tc-99m](HYNIC-HSA)(tricine)(2) showed the radioactivity levels at the injection site similar each other. These findings indicated that an addition of a macrophage binding function to Tc-99m-labeled HSA provided high and selective accumulation of the radioactivity in the SLN without affecting the elimination rate from the injection site. Such characteristics render [Tc-99m](HYNIC-NMA)(tricine)(2) attractive as a radiopharmaceutical for SLN identification. This study also demonstrated that the number of non-radiolabeled colloidal particles and the molar dose of mannosylated compounds play a crucial role in the SLN accumulation. (C) 2004 Elsevier Inc. All rights reserved.