**5.8. Apoptosis**

**Figure 2.** Representative PET-images of dynamic whole body acquisitions of a series of an allogeneically kidney trans‐ planted rat (POD 1 (A), 2 (B), 4 (C), and 7 (D), after tail vein injection of 18F-FDG. While the parenchyma (yellow circle) of renal allograft developing AR accumulates 18F-FDG with a maximum on post operative day (POD) 4, the native kid‐ ney (green circle) does not show any accumulation at any time. Please note that the renal pelvis can contain eliminat‐ ed 18F-FDG/18F-fluoride. Therefore, it has to be excluded from the measurements. Figure taken from [43]. Scale bar:

One step further, one cannot assess infiltrating leukocytes only but rather their tissue damag‐ ing activity by detection of activated matrix metalloproteinases (MMPs). Leukocyte-derived MMPs, like MMP-2 or MMP-9, were found to be active in AR [47;48]. Since MMP activity can be assessed using radiolabeled MMP-inhibitors in SPECT or PET this approach for detection of AR might be evaluated in future studies [49-52]. Maybe one can gather additional informa‐ tion regarding graft`s prognosis because MMPs are involved in tissue remodelling, too.

Acute tissue inflammations regardless of their origin present with a unique and challenging microenvironment including hypoxia (low oxygen), anoxia (complete lack of oxygen), hypo‐

icals. These conditions are characteristic features of inflamed tissues, along with the influx of leukocytes. In renal allografts, hypoxia and hypoxic adaptation are common within 2 weeks

concentration) and abundant free oxygen rad‐

percent injected dose

**5.7. Hypoxia**

**5.6. Matrix metalloproteinases**

96 Current Issues and Future Direction in Kidney Transplantation

glycemia (low blood glucose), acidosis (high H+

Apoptosis in AR is probably the result of different events occurring in AR. It may be a direct consequence of different cytokines discharged by leukocytes or directly provoked e.g. by CTLs. Within the inflammatory milieu of AR apoptosis might, among other factors, also be related to hypoxia, acidosis, or reactive oxygen species. Non-invasive detection of apoptosis in AR might be attractive because it may not serve for early detection of AR only, but also for mon‐ itoring of rejection kinetics and therapy response. Especially, early assessment of therapeutic success or failure is interesting to promptly adjust the therapeutic regimen. Likewise, quanti‐ fication of apoptosis might provide information regarding the extent of graft damage and therefore for its prognosis. However, small studies with different tracers targeting different steps in apoptosis have been performed in both, animal and man. A comprehensive review on detecting cell death *in vivo* has been recently published by us [55]. Two main operational strat‐ egies are followed. While imaging of caspases` activity using substrate-derived agents offers high selectivity, the detection of membrane phospholipid redistribution using extracellular agents has the advantage of high target density and accessibility [56]. We and others recently proposed different isatin analogues for 18F-labeling and detection of apoptosis [55]. However, studies detecting apoptosis in renal grafts using radiotracers for evaluation of their potential clinical value in AR have not been performed yet.
