Hexafluorobenzene in comparison with perfluoro‐15‐crown‐5‐ether for repeated monitoring of oxygenation using ¹⁹F MRI in a mouse model

Abstract

Hexafluorobenzene (HFB) and perfluoro-15-crown-5-ether (15C5) were compared as fluorine reporter probes of tissue oxygenation using (19)F MRI for dynamic assessment of muscle oxygenation, with special focus on muscle tissue toxicity of the probes, and consecutive alteration of animal behavior. The latter were also compared in terms of sensitivity to changes in oxygenation as well as of signal-to-noise ratio for accurate pO(2) measurements. For that purpose, mouse muscles were imaged at 11.7 T, at 2- and 36-h after intramuscular injection of HFB or 15C5. Histological analysis of the muscle tissue revealed a lack of toxicity for 15C5 from 2 up to 36-h postinjection, whereas HFB induced tissue necrosis, blood clots and thrombosis as soon as 24-h postinjection. This muscle toxicity led to a limitation in mice mobility 24-h after injection of HFB as evidenced by behavioral testing (open-field, grip strength, and catwalk tests), which was not the case after 15C5 intramuscular injection. Finally, pO(2) measurements assessed 2-h postinjection showed consistent values with both probes, evidencing cross-validation of the (19)F MRI oximetry technique for acute measurements. However, the measurement at 36-h was hampered for HFB, which showed significant lower values of muscle pO(2), whereas 15C5 was able to reliably assess muscle pO(2) at 36-h postinjection.

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

“…The 'intensity' parameter refers to the intensity of the paw prints that is detected by the system during gait and is related to weight support by the paws. Up to 5 runs were recorded per animal, and analysis was performed on the fastest uninterrupted run (<2s) by blinded experimenters (Mignion et al, 2013). The rats were trained 2 weeks before surgery, and the runs were recorded just before the surgery; 9 and 14 days; and 1, 2, and 3 months following surgery.…”

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation

“…PFCE was chosen for the probe because of its high oxygen sensitivity, high nuclear molarity (equivalent nuclei per volume), and excellent reported biocompatibility. 32,40 Fluorine-loaded fibrin gels were prepared with 75 mL of porcine plasma (Sigma-Aldrich) emulsified with 75 mL of PFCE. The mixture was emulsified by manual agitation, injected into a 40 mL immunoisolation device (TheraCyte, Inc., Laguna Hills, CA) using a 250-mL precision syringe (Hamilton Company, Reno, NV), and then cross-linked with 5% v/v bovine thrombin solution.…”

“…This study used temperature-compensating multiparametric calibrations to reduce measurement error. 27 Additionally, most previous 19 F-MRS oximetry studies evaluated PFCs directly injected into the tissue of interest 37,40 or intravenously into tumors that often have chaotic and ineffective vasculature, 27,28,30,31,34,35 which resulted in inhomogeneous distributions of the probes. An additional benefit of measuring pO 2 within TEGs, therefore, is the removal of limitations due to ineffectual probe delivery.…”

“…The most prevalent and promising PFC probes found in literature include perfluoro-15-crown-5-ether (PFCE), hexafluorobenzene (HFB), perfluorodecalin (PFD), perfluorooctyl bromide (PFOB), and perfluorotributylamine (PFTBA). 24,25,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] Hexamethyldisiloxane (HMDSO), a 1 H probe, has shown promise as well. 37,41 MRS methods utilizing these probes have been used to both measure and image oxygen in vivo, but have had limited clinical applications due to large measurement errors and difficulty with molecule delivery to target tissues.…”

Organic Nanoprobes for Fluorescence and 19F Magnetic Resonance Dual‐Modality Imaging

“…Alternatively, 19 F MRI holds several unique advantages such as low endogenous background signals, high signal-to-noise ratio (SNR), 100% natural isotopic abundance, relatively high sensitivity (83% of proton) and broad range of chemical shifts. [26][27][28][29] To date, some exogenous contrast agents such as molecular probes with a number of equivalent fluorine atoms, [27,[30][31][32][33][34][35] polymeric tracers containing high numbers of fluorine atoms, [28,[36][37][38][39][40][41][42] and fluorinated metallic nanoparticles [43][44][45][46] have been developed and employed for 19 F MRI. Despite great successes, it is highly desirable and still challenging to develop suitable 19 F MRI contrast agents with satisfied performance as well as multi-modalities.…”