Abstract

Introduction: Small diameter tissue-engineered arterial grafts (TEAGs) conjugated with rapamycin may improve TEAG outcomes by reducing early post-implant inflammatory responses, thereby improving rates of TEAG patency. Therefore, the objective of this study was to apply in vivo PET/CT imaging to compare inflammation and patency of TEAGs conjugated with or without rapamycin. We hypothesized that rapamycin-coated TEAGs would have reduced inflammation and improved patency rates that could be evaluated during a single imaging session using 18 F-FDG PET/CT imaging. Methods: Rapamycin coated (n=3) and non-rapamycin coated (n=3) TEAGs were unilaterally implanted in the carotid artery of juvenile lambs. Flourine-18 ( 18 F)-fluorodeoxyglucose (FDG) PET/CT imaging was performed 8 weeks after TEAG implantation to quantify inflammation of the graft, which was expressed as the maximum standardized uptake value (SUV max ) in the graft. Graft patency was assessed using co-registered CT angiography imaging. In vivo PET/CT imaging results were further evaluated by ex vivo gamma counting of 18 F-FDG uptake in TEAG tissue. Results: In vivo PET/CT detected qualitative and quantitative differences in inflammation between non-drug coated and drug coated TEAGs (SUV max : 6.18±1.67 vs, 4.25±0.81; p=0.1). Differences in inflammation between groups were significant when evaluating results of ex vivo gamma counting of 18 F-FDG uptake (% Injected dose/g: 0.86±0.10 vs, 0.50±0.010; p=0.003). Additionally, CT angiography demonstrated that all rapamycin-coated TEAGs were patent (3/3) at 8 weeks post-implant whereas only one non-drug coated TEAG remained patent (1/3). Conclusions: Conjugation of TEAGs with rapamycin prevents excessive inflammation in the early months after implantation and maintains graft patency. PET/CT offers a translatable imaging approach that allows for combined in vivo assessment of the functional and anatomical characteristics of TEAGs and may assist in optimizing scaffold design for next-generation TEAGs.

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