Pharmacokinetic Properties of 68Ga-Labelled Folic Acid Conjugates: Improvement Using HEHE Tagстатья
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Дата последнего поиска статьи во внешних источниках: 2 сентября 2020 г.
Аннотация:The folate receptor (FR) is a promising cell membrane-associated target for molecularimaging 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 ofepithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthytissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Extremelyhigh undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback ofFR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulationof folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into theirstructure. Two folic acid based compounds were synthesized: NODAGA-1,4-butanediamine-folicacid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2fragment. In vitro studies with FR (+) cells (KВ and others) showed that both compounds havespecificity 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 bearinganimals, were carried out. The results showed that introduction of the (HE)2 tag into the structureof folate radioconjugates can significantly reduce the accumulation of these compounds innon-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.