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.

BACKGROUND: We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman 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. METHODS: Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 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. RESULTS: At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether 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. CONCLUSIONS: The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.

Long-Term Management of Vascular Access Ports in Nonhuman Primates Used in Preclinical Efficacy and Tolerability Studies.

Vascular access ports (VAPs) are an essential tool for long-term vascular access in preclinical studies and disease modeling in non-human primates (NHPs). We retrospectively reviewed central (inferior vena cava, IVC) and portal VAP implantation with the maintenance at our center from 15 January 2010 to 31 January 2018. In total, 209 VAPs were implanted for long-term drug administration and sampling. Patency was >95% at 6 months and >80% at 1 year for IVC VAPs and >90% at 6 months and >85% at 1 year for portal VAPs. The majority of animals had no complications and access was generally durable with device use ranging up to 7 years. In IVC, VAPs loss of patency occurred in 13% (0.035/100 d), surgical site infection in 2.9% (0.097/100 d), port pocket infection in 2.2% (0.004/100 d), erosion in 2.9%, 0.008/100 d), and mechanical failure in 4.3% (0.012/100 d). In portal, VAPs loss of patency occurred in 11.3% (0.028/100 d) and port pocket infection in 1.4% (0.003/100 d). About 12% of VAPs were removed as a result of complications.This study confirms VAP implant and maintenance is a beneficial and safe practice in NHPs resulting in favorable outcomes. High patency rates and low complication rates are comparable to the clinical setting. In addition to enabling comprehensive data collection, VAPs increase satisfaction and well-being by minimizing interference with daily routines and fostering cooperation. VAP implantation, together with an effective maintenance regimen and co-operative handling, is a reliable and convenient refined method for drug administration and blood sampling.Keywords: Vascular access port; nonhuman primates; refinement; central vascular access; portal vascular access; surgical technique; experimental surgery; animal model.