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Radionuclide Imaging of Acute Lung Transplant Rejection With Annexin V^*

^* From the Departments of Radiology/Division of Pediatric Radiology (Dr. Blankenberg), Cardiothoracic Surgery (Drs. Robbins, Vriens, and Mr. Stoot), Pathology (Dr. Berry), and Radiology/Division of Nuclear Medicine (Dr. Strauss), Stanford University School of Medicine, Stanford, CA; and the Department of Laboratory Medicine (Dr. Tait), University of Washington, Seattle, WA.

Correspondence to: Francis G. Blankenberg, MD, Department of Radiology/Division of Pediatric Radiology, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305-5105; e-mail: MA.FRB{at}forsythe.stanford.edu

Study objectives: Early detection and treatment of lung transplant rejection is critical for preservation of pulmonary graft function. Damage to pulmonary allografts is mediated by apoptotic cell death induced by the alloreactive T lymphocytes that infiltrate lung grafts. Previous studies demonstrate that acute cardiac allograft rejection can be visualized using radiolabeled annexin V. This study was done to determine whether this technique could visualize acute rejection in a rodent model of unilateral orthotopic lung transplantation.

Design: Eighteen Sprague-Dawley ACI rats underwent removal of their left lung followed by orthotopic transplant of either an allogeneic (PVG, immunologically mismatched; N = 10) or a syngeneic (ACI, immunologically matched) pulmonary graft (N = 8). Animals were imaged 1 h after IV injection of 1 mCi (37.0 MBq) of ^99mTc-annexin V 1 to 7 days after transplantation.

Results: Lungs receiving the allograft demonstrated moderate to marked mononuclear infiltration of the perivascular, interstitial, and peribronchial tissues. No mononuclear infiltrates were noted in the native right lungs nor in the syngeneic transplants. Region of interest image analysis revealed significant (p < 0.0005) increases of transplant to normal lung activity ratios 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 noninvasively identified using ^99mTc-annexin V. Radiolabeled annexin V may be a clinically useful noninvasive screening tool for acute rejection.

Key Words: acute rejection • apoptosis • lymphocytes • organ transplantation • pulmonary • radionuclide imaging

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