**7. Apoptosis imaging heart transplantation**

Acute rejection remains a limiting factor of cardiac transplantation. The histopathologic manifestation of transplant rejection comprises perivascular and interstitial mononuclear inflammatory cell infiltration associated with myocyte apoptosis and necrosis. To monitor the acute rejection, endomyocardial biopsies are required frequently. Current guidelines recommend 15-20 endomyocardial biopsies in the first year after transplantation to monitor potential allograft rejection. However, invasive endomyocardial biopsy may be associated with a small risk of complications. If non-invasive imaging for the detection of transplant rejection is feasible, endomyocardial biopsies might be reduced.

Study with rat model of allograft rejection demonstrated that significant 99mTc-annexin V uptake correlated well with the histologic grade of rejection and scattered positive TUNEL stainings were observed in graft-infiltrating inflammatory cells, endothelial cells, and myocytes. In addition, after the treatment of rejection with cyclosporine, no TUNEL positivity was observed and 99mTc-annexin V uptake decreased to baseline (Vriens, et al., 1998). In 18 patients with cardiac allograft recipients, 5 had positive myocardial uptake of 99mTc-annexin V at 1 h after the tracer injection and all these 5 patients showed at least moderate transplant rejection and caspase-3 staining in their biopsy specimens. On the other hand, 11 of 13 patients with no cardiac uptake of 99mTc-annexin V demonstrated no finding of rejection and other 2 patients showed only focal lymphomononuclear cell infiltration (Narula, et al., 2001). In another clinical study with 10 patients with cardiac transplant, 2 patients with moderate acute rejection by endomyocardial biopsy showed significant 99mTcannexin V uptake, however, specificity was suboptimal with 4 of 8 patients without rejection demonstrating significant 99mTc-annexin V uptake.

All these animal and clinical studies revealed that the apoptosis imaging has potential to noninvasively identify patients with transplant rejection and monitor the response to immune modulation therapy.
