title: Injectable LiNc-BuO loaded microspheres as in vivo EPR oxygen sensors after co-implantation with tumor cells.
abstract: Electron paramagnetic resonance (EPR) oximetry is a technique which allows accurate and repeatable oxygen measurements. We encapsulated a highly oxygen sensitive particulate EPR spin probe into microparticles to improve its dispersibility and, hence, facilitate the administration. These biocompatible, non-toxic microspheres contained 5-10 % (w/w) spin probe and had an oxygen sensitivity of 0.60 ± 0.01 µT/mmHg. To evaluate the performance of the microparticles as oxygen sensors, they were co-implanted with syngeneic tumor cells in 2 different rat strains. Thus, tissue injury was avoided and the microparticles were distributed all over the tumor tissue. Dynamic changes of the intratumoral oxygen partial pressure during inhalation of 8 %, 21 %, or 100 % oxygen were monitored in vivo by EPR spectroscopy and quantified. Values were verified in vivo by invasive fluorometric measurements using Oxylite probes and ex vivo by pimonidazole adduct accumulation. There were no hints that the tumor physiology or tissue oxygenation had been altered by the microparticles. Hence, these microprobes offer great potential as oxygen sensors in preclinical research, not only for EPR spectroscopy but also for EPR imaging. For instance, the assessment of tissue oxygenation during therapeutic interventions might help understanding pathophysiological processes and lead to an individualized treatment planning or the use of formulations with hypoxia triggered release of active agents.
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Frank
authors.affiliation: Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 6, 06112 Halle (Saale), Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gündel
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Drescher
authors.affiliation: Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, Magdeburger Str. 6, 06112 Halle (Saale), Germany. Electronic address: oliver.thews@medizin.uni-halle.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Thews
authors.affiliation: Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany. Electronic address: karsten.maeder@pharmazie.uni-halle.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000818:Animals; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008856:Microscopy, Fluorescence; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000473:pathology*; D010100:Oxygen / Q000032:analysis*; D011166:Porphyrins; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
chemical_list: D011166:Porphyrins; D013113:Spin Labels; C487013:lithium octa-n-butoxynaphthalocyanine; D010100:Oxygen
keywords: Biocompatibility; EPR; ESR; Encapsulation; LiNc-BuO; Microparticles; Oximetry; Oxygen sensor; Pimonidazole; Tumor