**5.4. Imaging using** *in vivo* **radiolabeled leukocytes**

At present only a few preclinical and clinical studies are published dealing with labeled leu‐ kocytes and detection of AR in intestine, hearts, pancreas islets and skin. Only one study per‐ formed in a small cohort of kidney transplant recipients evaluated 99mTc-mononuclear cell scintigraphy for diagnosis of AR. In this study, the authors were able to show that AR was diagnosed correctly and successfully discriminated from ATN [39]. In a further development of their approach, we established leukocyte PET imaging using very low amounts of 18F-FDG for the diagnosis of AR in a rat kidney transplant model. *Ex vivo* 18F-FDG labeled human CTLs were able to diagnose renal AR within a time frame of 1 h after application and discriminate AR from important differential diagnoses such as acute cyclosporine toxicity or ATN (*Grabner*

**Figure 1.** Representative PET-images of dynamic whole body acquisitions of a series of an allogeneically kidney trans‐ planted rat on postoperative day 4 60 min and 120 min after tail vein injection of 30 x 10618F-FDG labeled CTL. While the parenchyma (yellow circle) of renal allograft developing AR accumulates 18F-FDG-CTLs, the native kidney (green circle) does not show any accumulation at any time. Please note that the renal pelvis can contain eliminated 18F-FDG/

Since infiltration of leukocytes, especially CTLs, in allografts appears before physiologic or mechanical manifestations of organ dysfunction is apparent, nuclear imaging employing leu‐

kocytes might be a promising tool for specific, sensitive and early detection of AR.

18F-fluoride. Therefore, it has to be excluded from the measurements. ID: injected dose

*et al. in press*) (Fig. 1).

94 Current Issues and Future Direction in Kidney Transplantation

Instead of employing *ex vivo* labeled leukocytes, radiolabeled monoclonal antibodies (frag‐ ments) (mAbs) have been established for detection of leukocyte (related) antigens. Their ad‐ vantages include standardized production, easier storage and handling, while they are highly specific for their target leading to a good background/target ration. However, limitations might be the targeting of extravascular antigens and potential but rare allergic complications, when using the antibodies in a patient.

As discussed, CTLs are the major cell type involved in AR. Martins *et al.* used 99mTc-OKT3 targeting CTLs in recipients of renal transplants [40]. In their preliminary results they state that out of 22 patients they successfully identified 3 patients with AR using 99mTc-OKT3 scans. Apparently, their results published in 2004 have to be confirmed in further studies. A recently published attractive, being somehow better biocompatible, alternative might be CD3 targeting 99mTc-SHNH-visilizumab which needs to be evaluated in the future [41].
