No abstract

The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthy tissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Extremely high undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback of FR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulation of folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into their structure. Two folic acid based compounds were synthesized: NODAGA-1,4-butanediamine-folic acid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2 fragment. In vitro studies with FR (+) cells (KB and others) showed that both compounds have specificity for FR. Introduction of (HE)2-tag does not affect FR binding ability of the conjugates. In vivo biodistribution studies with normal laboratory animals, as well as with KB tumor bearing animals, were carried out. The results showed that introduction of the (HE)2 tag into the structure of folate radioconjugates can significantly reduce the accumulation of these compounds in non-target tissues and important organs (the accumulation in the kidneys is reduced 2–4 times), leaving the accumulation in tumor at least at the same level, and even increasing it.

No abstract

The radiopharmaceutical precursor «Oxind, 111In» is a complex compound for labeling autologous leukocytes of human blood and their subsequent introduction for non-specific visualization and localization of inflammation foci of different nature by single-photon emission computed tomography (SPECT). The cytotoxic effect of lyophilisate for preparation of radiopharmaceutical preparation «Oxind, 111In» and its radiopharmaceutical precursor on rabbit blood leukocytes has been investigated. In the course of studies of the cytotoxicity of the lyophilisate for the preparation of a radiopharmaceutical precursor with successively increasing concentrations of the main substance, 8-hydroxyquinoline, the permissible concentrations have been determined and the absolutely cytotoxic concentration was achieved.In the study of the cytotoxic effect of the precursor of radiopharmaceutical on two dosages that differ by 10 times in volume activities (MBq / ml), the absence of cytotoxic effects has been confirmed.