Universität zu Köln

Grievink, Hilbert, Shamni, Ofer ORCID: 0000-0001-9277-6137, Krajewski, Seweryn, Steczek, Lukasz, Grundemann, Dirk, Mishani, Eyal and Abourbeh, Galith (2022). Organic Cation Transporter-Mediated Accumulation of Quinolinium Salts in the LV Myocardium of Rodents. Mol. Imaging. Biol., 24 (5). S. 1 - 10. NEW YORK: SPRINGER. ISSN 1860-2002

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Abstract

Purpose: Quaternary ammonium salts have demonstrated marked accumulation in the left ventricular (LV) myocardium of rodents and swine. To investigate the mechanism underlying this uptake, the present study examined the interaction of [F-18]fluoroethylquinolinium ([F-18]FEtQ) with the family of organic cation transporters (OCTs). Procedures: The cellular uptake of [F-18]FEtQ into HEK293 cells, expressing human OCT1, -2, or -3 (HEK293-hOCT), and its inhibition by corticosterone was evaluated in vitro. The inhibitory effect of decynium 22 (D 22) in vivo was also studied, using PET/CT of HEK293-hOCT tumor-bearing mice. Furthermore, the distribution kinetics of [F-18]FEtQ were determined in rats, with and without pre-administration of corticosterone, and following administration to a non-human primate (NHP). Results: The accumulation of [F-18]FEtQ in HEK293-hOCT cells was 15-20-fold higher than in control cells and could be inhibited by corticosterone. in vivo, the uptake of [F-18]FEtQ in the LV myocardium of corticosterone-treated rats was significantly reduced compared to that of untreated animals. Similarly, following administration of D 22 to HEK293-hOCT tumor-bearing mice, the peak tumor uptake of [F-18] FEtQ was reduced by 40-45 % compared to baseline. Contrary to the distinct accumulation of [F-18]FEtQ in the LV myocardium of rats, no cardiac uptake was observed following its administration to a NHP. Conclusions: The quinolinium salt derivative [F-18]FEtQ interacts with the family of OCTs, and this interaction could account, at least in part, for the increased uptake in the LV myocardium of rodents. Nonetheless, its low affinity for hOCT3 and the results of PET/CT imaging in a NHP indicate a limited clinical applicability as a radiopharmaceutical for cardiac and/or OCT imaging.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Grievink, Hilbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Shamni, Ofer UNSPECIFIED orcid.org/0000-0001-9277-6137 UNSPECIFIED Krajewski, Seweryn UNSPECIFIED UNSPECIFIED UNSPECIFIED Steczek, Lukasz UNSPECIFIED UNSPECIFIED UNSPECIFIED Grundemann, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Mishani, Eyal UNSPECIFIED UNSPECIFIED UNSPECIFIED Abourbeh, Galith UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-672931
DOI:	10.1007/s11307-022-01728-y
Journal or Publication Title:	Mol. Imaging. Biol.
Volume:	24
Number:	5
Page Range:	S. 1 - 10
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1860-2002
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE DISTRIBUTION; 3 SLC22A3; OXALIPLATIN; EXPRESSION; AMMONIUM; HOCT2 Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67293