Kevin P Daly1, Jason L J Dearling, Tatsuichiro Seto, Patricia Dunning, Frederic Fahey, Alan B Packard, David M Briscoe. 1. 1 Transplant Research Program, Boston Children's Hospital. 2 Department of Cardiology, Boston Children's Hospital, Boston, MA. 3 Department of Pediatrics, Harvard Medical School, Boston, MA. 4 Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Boston Children's Hospital, Boston, MA. 5 Department of Radiology, Harvard Medical School, Boston, MA. 6 Division of Nephrology, Department of Medicine, Boston Children's Hospital, Boston, MA.
Abstract
BACKGROUND: Positron emission tomography (PET) has the potential to be a specific, sensitive and quantitative diagnostic test for transplant rejection. To test this hypothesis, we evaluated F-labeled fluorodeoxyglucose ([F]FDG) and N-labeled ammonia ([N]NH3) small animal PET imaging in a well-established murine cardiac rejection model. METHODS: Heterotopic transplants were performed using minor major histocompatibility complex-mismatched B6.C-H2 donor hearts in C57BL/6(H-2) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls. [F]FDG PET imaging was performed weekly between posttransplant days 7 and 42, and the percent injected dose was computed for each graft. [N]NH3 imaging was performed to evaluate myocardial perfusion. RESULTS: There was a significant increase in [F]FDG uptake in allografts from day 14 to day 21 (1.6% to 5.2%; P < 0.001) and uptake in allografts was significantly increased on posttransplant days 21 (5.2% vs 0.9%; P = 0.005) and 28 (4.8% vs 0.9%; P = 0.006) compared to isograft controls. Furthermore, [F]FDG uptake correlated with an increase in rejection grade within allografts between days 14 and 28 after transplantation. Finally, the uptake of [N]NH3 was significantly lower relative to the native heart in allografts with chronic vasculopathy compared to isograft controls on day 28 (P = 0.01). CONCLUSIONS: PET imaging with [F]FDG can be used after transplantation to monitor the evolution of rejection. Decreased uptake of [N]NH3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [F]FDG and [N]NH3 PET imaging could be used as a noninvasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients.
BACKGROUND: Positron emission tomography (PET) has the potential to be a specific, sensitive and quantitative diagnostic test for transplant rejection. To test this hypothesis, we evaluated F-labeled fluorodeoxyglucose ([F]FDG) and N-labeled ammonia ([N]NH3) small animal PET imaging in a well-established murine cardiac rejection model. METHODS: Heterotopic transplants were performed using minor major histocompatibility complex-mismatched B6.C-H2 donor hearts in C57BL/6(H-2) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls. [F]FDG PET imaging was performed weekly between posttransplant days 7 and 42, and the percent injected dose was computed for each graft. [N]NH3 imaging was performed to evaluate myocardial perfusion. RESULTS: There was a significant increase in [F]FDG uptake in allografts from day 14 to day 21 (1.6% to 5.2%; P < 0.001) and uptake in allografts was significantly increased on posttransplant days 21 (5.2% vs 0.9%; P = 0.005) and 28 (4.8% vs 0.9%; P = 0.006) compared to isograft controls. Furthermore, [F]FDG uptake correlated with an increase in rejection grade within allografts between days 14 and 28 after transplantation. Finally, the uptake of [N]NH3 was significantly lower relative to the native heart in allografts with chronic vasculopathy compared to isograft controls on day 28 (P = 0.01). CONCLUSIONS: PET imaging with [F]FDG can be used after transplantation to monitor the evolution of rejection. Decreased uptake of [N]NH3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [F]FDG and [N]NH3 PET imaging could be used as a noninvasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients.
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