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, non-rejecting isografts, and rejecting allografts were evaluated. Decay-corrected uptake of 13NH 3 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 0.77% ± 0.4%; p < 0.02) and mild rejection (2.1% ± 0.6% versus 0.4% ± 0.1%; p < 0.02). Uptake of NH 3 in severely rejected grafts is reduced compared with nonrejecting grafts (0.6% ± 0.3% versus 1.7% ± 1.1%; p < 0.02). There is no difference in NH 3 uptake during mild rejection (1.8% ± 0.7% versus 1.3% ± 0.3%; p > 0.05). Uptake of FDG and NH 3 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.