Noninvasive detection of heart transplant rejection with positron emission scintigraphy

Positron emission tomography has recently been used to evaluate ischemic heart disease through changes in myocardial blood flow and carbohydrate metabolism. Positron-emitting tracers were evaluated for their ability to detect acute allograft rejection after heterotopic cardiac transplantation in the rat. Sham-operated controls, nonrejecting isografts, and rejecting allografts were evaluated. Decay-corrected uptake of 13NH3 and 18F 2-fluoro 2-deoxyglucose (FDG) reflects blood flow and glucose flux, respectively. Histologic examination of rejecting allografts documented mild rejection at 4 days and severe acute rejection by 8 days. All isografts were free from rejection. Uptake of FDG is greater in rejecting allografts than in nonrejecting isografts during both severe rejection (2.4% +/- 0.8% versus 0.7% +/- 0.4%; p less than 0.02) and mild rejection (2.1% +/- 0.6% versus 0.4% +/- 0.1%; p less than 0.02). Uptake of NH3 in severely rejected grafts is reduced compared with nonrejecting grafts (0.6% +/- 0.3% versus 1.7% +/- 1.1%; p less than 0.02). There is no difference in NH3 uptake during mild rejection (1.8% +/- 0.7% versus 1.3% +/- 0.3%; p greater than 0.05). Uptake of FDG and NH3 in native hearts of animals from all experimental groups is not significantly different from that in sham-operated controls. Glucose may be a preferred metabolic substrate during rejection. Our data support a humoral mechanism for substrate preference during transplant rejection and a potential diagnostic role for positron emission tomography.