Pharmacokinetic Properties of 68Ga-Labelled Folic Acid Conjugates: Improvement Using HEHE Tag

Larenkov, A.; Rakhimov, M.; Lunyova, K.; Klementyeva, O.; Maruk, A.; Machulkin, A.

Авторы: Anton Larenkov, Marat Rakhimov, Kristina Lunyova, Olga Klementyeva, Alesya Maruk, Aleksei Machulkin
Журнал: Molecules
Том: 25
Номер: 11
Год издания: 2020
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 2712
DOI: 10.3390/molecules25112712
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.
Добавил в систему: Мачулкин Алексей Эдуардович

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Pharmacokinetic Properties of 68Ga-Labelled Folic Acid Conjugates: Improvement Using HEHE Tagстатья

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