Daly Kevin P, Dearling Jason L J, Seto Tatsuichiro, Dunning Patricia, Fahey Frederic, Packard Alan B, Briscoe David M
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.
Transplantation. 2015 Sep;99(9):e132-9. doi: 10.1097/TP.0000000000000618.
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.
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.
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).
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.
正电子发射断层扫描（PET）有潜力成为一种用于移植排斥反应的特异性、敏感性和定量诊断测试。为验证这一假设，我们在一个成熟的小鼠心脏排斥模型中评估了F标记的氟脱氧葡萄糖（[F]FDG）和N标记的氨（[N]NH3）小动物PET成像。
使用次要主要组织相容性复合体不匹配的B6.C-H2供体心脏在C57BL/6（H-2）受体中进行异位移植。将C57BL/6供体心脏移植到C57BL/6受体中作为同基因移植对照。在移植后第7天至第42天每周进行一次[F]FDG PET成像，并计算每个移植物的注射剂量百分比。进行[N]NH3成像以评估心肌灌注。
从第14天到第21天，同种异体移植物中[F]FDG摄取显著增加（从1.6%增加到5.2%；P < 0.001），与同基因移植对照相比，移植后第21天（5.2%对0.9%；P = 0.005）和第28天（4.8%对0.9%；P = 0.006）同种异体移植物的摄取显著增加。此外，在移植后第14天至第28天期间，同种异体移植物中[F]FDG摄取与排斥反应等级的增加相关。最后，在第28天，与同基因移植对照相比，患有慢性血管病变的同种异体移植物中[F]FDG摄取相对于天然心脏显著降低（P = 0.01）。
移植后可使用[F]FDG进行PET成像以监测排斥反应的进展。排斥性同种异体移植物中[F]FDG摄取降低可能反映心肌血流减少。这些数据表明，联合使用[F]FDG和[F]NH3 PET成像可作为一种无创、定量技术用于连续监测同种异体移植排斥反应，并在人类移植受者中具有潜在应用价值。
