Radionuclide imaging of acute lung transplant rejection with annexin V

Study objectives: Early detection and treatment of lung transplant rejectio n is critical for. preservation of pulmonary graft function. Damage to pulm onary allografts is mediated by apoptotic cell death induced by the allorea ctive T lymphocytes that infiltrate lung grafts. Previous studies demonstra te that acute cardiac allograft rejection can be visualized using radiolabe led annexin V. This study was done to determine whether this technique coul d visualize acute rejection in a rodent model of unilateral orthotopic long transplantation. Design: Eighteen Sprague-Dawley ACI rats underwent removal of their left lu ng followed by orthotopic transplant of either an allogeneic (PVG, immunolo gically mismatched; N = 10) or a syngeneic (ACI, immunologically matched) p ulmonary graft (N = 8). Animals were imaged 1 h after IV injection of 1 mCi (37.0 MBq) of Tc-99m-annexin V 1 to 7 days after transportation. Results: Lungs receiving the allograft demonstrated moderate to marked mono nuclear infiltration of the perivascular, interstitial, and peribronchial t issues. No mononuclear infiltrates were noted in the native right lungs nor in the syngeneic transplants. Region of interest image analysis revealed s ignificant (p < 0.0005) increases of transplant to normal lung activity rat ios 3 to 7 days after allograft surgery. The increased annexin V uptake in these lungs was confirmed at biodistribution assay (allograft 151% greater than isograft activity, p < 0.005). Conclusions: Acute experimental lung transplant rejection can be noninvasiv ely identified using Tc-99m-annexin V. Radiolabeled annexin V may be a clin ically useful noninvasive screening tool for acute rejection.