Pretargeting articulation for improving the deliverance of injected dose to the tumor: An evaluation of In vivo study for enhanced tumor uptake

Abstract

Background: Radiobioconjugate targeting using monoclonal antibodies linked to a high-energy radionuclide is a promising approach for treating metastatic cancer. The central problem of radiobioconjugate targeting is the small fraction of radiobioconjugate localized in the tumor. Pretargeting based on avidin–biotin approach has been recommended to maximize tumor targeting. The current study was conceded with an aim to assess a selective targeting strategy for the site-specific deliverance of an injected radioactive dose to the tumor cells. Methods: Two labeling protocols were tested and evaluated, both for the direct and indirect radiolabeling of antibodies with radionuclide technetium. A comparative evaluation of biodistribution studies relating to the deposition of injected dose in different organs was carried out in tumor-bearing nude mice both for a direct single-step and indirect multistep pretargeting approach. Results: High concentration of the injected dose was accounted in the nontarget organs and blood for a direct targeting mode, as compared to indirect multistep pretargeting with high tumor uptake. Better tumor visibility and high tumor/nontumor ratio were observed at 24 h and 48 h. However, a considerable deposition of radioactivity in the organs such as liver, spleen, kidney, and lungs as a nonspecific, reticuloendothelial system uptake was observed as a cause of concern and the use of certain blocking agents were explored, effective for reducing the same. Conclusions: The study demonstrates a successful targeting efficiency of the radiolabeled bioconjugate for technetium (Tc-99m), through a multistep pretargeting approach, and the same can be applied for other related therapy radionuclides also.