Biodistribution and kinetic characters of radiopharmaceutical medication based on biospecific antibodies to tumor-associated stroma elements and 177lutcium

Biodistribution and kinetics were studied of potentially target biospecific radiopharmaceutical medication for the treatment of malignant tumors of various histologic type and location with expression of cytotoxic T-lymphocyte membrane associated glycoprotein 4 and glucocorticoid Induced Tumor Necrosis Factor Receptor) 177Lu-DOTA-anti-CTLA4-GITR. Colorectal cancer experimental model has been successfully reproduced by means of murine large intestine experimental adenocarcinoma cells (AKATOL) СТ26 EGFR) direct transplantation. The model was characteristic of moderate growth rate and practically complete absence of metastatic spread. Immunohistochemical assay of tumor tissue has revealed satisfactory expression level of target antigens for the medication under study, i.e. cytotoxic T-lymphocyte associated protein 4 (CTLA4) as well as membrane receptor of tumor necrosis factor group (GITR). This medication 177Lu-DOTA-anti-CTLA4-GITR has been shown to store in the tumor tissue. Its major pathways out of the organism were through urinary system. On the other hand, the medication has also been demonstrated to store in non-target tissues, namely: kidneys, liver, large intestine. The results of this study may be used in preclinical studies of medications and serve as a basis for broader studies of 177Lu-DOTA-anti-CTLA4-GITR and its safety.