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 18 F-labeled fluorodeoxyglucose ([18 F] FDG) and 13 N-labeled ammonia ([13 N] NH 3) 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 bm12 donor hearts in C57BL/6 (H-2 b) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls.[18 F] FDG PET imaging was performed weekly between posttransplant days 7 and 42, and the percent injected dose was computed for each graft.[13 N] NH 3 imaging was performed to evaluate myocardial perfusion.

Results

There was a significant increase in [18 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,[18 F] FDG uptake correlated with an increase in rejection grade within allografts between days 14 and 28 after transplantation. Finally, the uptake of [13 N] NH 3 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 [18 F] FDG can be used after transplantation to monitor the evolution of rejection. Decreased uptake of [13 N] NH 3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [18 F] FDG and [13 N] NH 3 PET imaging could be used as a noninvasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients.