Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.
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We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally (i.p,) in healthy non-human primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes.Perfluoro-15-crown-5-ether (PFCE) alginate capsules were infused i.p. into three healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using F-MR relaxometry (F-MRR) and a fiber optic probe. F-MR imaging (F-MRI) was used to determine the locations of capsules within the peritoneal space on Days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem.At Day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site and the pO2 measurement using MRR was147 ± 9 mmHg). On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mmHg. Measurements using the fiber optic oxygen sensor were 132 ± 7.5 mmHg (Day 0) and 89 ± 6.1 mmHg (Day 7). PFCE capsules retrieved on Day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20 B cells, CD4 and CD8 T cells, and CD14 macrophages increased consistent with a mild foreign body reaction.The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted i.p.
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