Studying the biological feasibility of [⁹⁹mTc(CO)₃]-dextran-cysteine-cysteine-mannose as a potential molecular radiopharmaceutical for sentinel node detection.

Khan, Irfan U; Shahid, Abubaker; Ahmad, Fayyaz; Dar, Ume K; Ahmad, Munir; Javed, Muhammad

OBJECTIVE The aim of this work was to radiolabel and bioevaluate the technetium-99m labeled dextran dicysteine mannose (DCCM) [(99m)Tc(CO)₃]-DCCM for sentinel lymph node detection. METHODS Dextran dicysteine mannose was radiolabeled using the carbonyl method. Various parameters were studied such as in vitro stability at room temperature up to 5 h, protein binding and partition coefficient. Bioevaluation was performed in a rabbit model by developing images under a gamma camera at various time intervals. Biodistribution was performed in Wistar rat models (n = 3) by dissection and measurement of percent injected dose in various body organs, at 60 and 180 min post-injection intervals. Biodistribution was performed in two different groups of animals: in the first group, the radiolabeled compound was injected at a concentration of 200 μg/ml, thus delivering 10 μg radiolabeled compound at the site of injection; in the second group, the radiolabeled compound was injected at a concentration of 50 μg/ml, delivering 2.5 μg radiolabeled compound at the site of injection. RESULTS Radiolabeling efficacy was 97.5 ± 1% which remained quite stable till 5 h. Protein binding data show that 71.1 ± 5% drug exhibited binding with blood proteins. Partition coefficient results show that our radiopharmaceutical is quite hydrophilic in nature. It can be inferred from the imaging data that sentinel node can be visualized within 30 min post-injection. Rat dissection data showed that when the radiolabeled compound was injected at a concentration of 50 μg/ml, at 60 min post-injection, ~2.85% of activity was retained in the sentinel node with a significantly less accumulation, e.g., ~0.12%, in the secondary node, which resulted in very high popliteal extraction (PE) value, e.g., ~98%. At 180 min post-injection, 2.46 ± 0.29 % was found to be retained in the sentinel node and PE (99.64 ± 0.23%), thus resulting in almost complete washout from the secondary node (0.05 ± 0.01%). CONCLUSION The study demonstrates that radiolabeled DCCM might be a successful radiopharmaceutical for sentinel node detection.