Conjugation of antibodies with radiogold nanoparticles, as an effector targeting agents in radiobioconjugate cancer therapy: Optimized labeling and biodistribution results

Pankaj Garg, Daya Kishore Hazra

Indian Journal of Nuclear Medicine 2017 32(4):296-303

Purpose of the Study: Drug accessibility to the tumor cells is an important area of concern with an anticipation of increasing the efficacy of the drug to be delivered to a specific site. The biogenesis of gold nanoparticles using plant-mediated phytochemical extracts and their possible linkage to cancer antibodies with an aim at delivering the conjugate specifically to the tumor-associated antigen is the basic objective of the research. Materials and Methodology: Radiolabeling of antibodies with gold nanoparticles was carried out by a protocol, and the labeling extent of antibodies was compared with that of a radiogold solution to ordinary particulate size (AuNO-Ab). The amount of radiolabeling was estimated by subjecting the reaction mixtures to thin layer chromatography (ITLC-Silica-gel) in different solvent mediums, both by visual inspection of images of the Siemens Orbitor Gamma Camera ZLC-7500 and also by in vitro counting of the radioactive counts in different quarters of the chromatographic strips. Biodistribution relating to the deposition of injected dose in nontargeting sites (reticuloendothelial system [RES]-localization) was studied and efforts were made for reducing the same. Results: Much improved gold incorporation was confirmed at various molar ratios of gold to immunoglobulin (antibody) using nanogold solution (>85%). The RES uptake in the liver, spleen etc., was observed as a problem and the prior administration of unlabeled nonspecific gammaglobulin (before the actual radiolabeled product) was identified as the suitable blocking agent for this purpose. Conclusion: The study signifies the potential for PEGylated gold nanoparticles of a precise size range, suitable to use as a delivery vehicle for targeting small biomolecules (antibody etc.) to the tumor site. The stability of this labeled immunoconjugate and other toxicity effects under physiological conditions needs further evaluation. If successful, this could be a role model for attaining high tumor/nontumor ratio.

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