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Cell Biochem Biophys. 2018 Jun;76(1-2):19-28. doi: 10.1007/s12013-017-0824-3. Epub 2017 Sep 4.

EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.

Author information

1
NanoBioMedical Centre, Adam Mickiewicz University, ul. Umultowska 85, 61614, Poznań, Poland. agnbos@amu.edu.pl.
2
Faculty of Physics, Adam Mickiewicz University, ul. Umultowska 14, 61614, Poznań, Poland. agnbos@amu.edu.pl.
3
NanoBioMedical Centre, Adam Mickiewicz University, ul. Umultowska 85, 61614, Poznań, Poland.
4
Faculty of Physics, Adam Mickiewicz University, ul. Umultowska 14, 61614, Poznań, Poland.
5
Department of Toxicology, Poznan University of Medical Sciences, ul. Dojazd 30, 60631, Poznan, Poland.
6
Faculty of Pharmacy, Suez Canal University, P.O. 41522, Ismailia, Egypt.
7
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany.
8
NanoBioMedical Centre, Adam Mickiewicz University, ul. Umultowska 85, 61614, Poznań, Poland. krztad@amu.edu.pl.
9
Institute of Molecular Physics, Polish Academy of Sciences, ul. M. Smoluchowskiego 17, 60179, Poznań, Poland. krztad@amu.edu.pl.

Abstract

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

KEYWORDS:

Cytotoxicity; EPR oximetry; Oxygenation sensor; TAM derivative

PMID:
28871484
PMCID:
PMC5913390
DOI:
10.1007/s12013-017-0824-3
[Indexed for MEDLINE]
Free PMC Article

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