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Annexin-V imaging for noninvasive detection of cardiac allograft rejection

Nature Medicine volume 7, pages 1347–1352 (2001)Cite this article

Abstract

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

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Figure 1: Noninvasive imaging with 99mTc–annexin-V.
Figure 2: Diffuse myocardial uptake of 99mTc–annexin-V in cardiac allograft.
Figure 3: Pathologic characterization of EMB specimens.

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Authors and Affiliations

  1. Hahnemann University Hospital, Philadelphia, Pennsylvania, USA

    Jagat Narula, Elmo R. Acio, Louis E. Samuels, Billy Fyfe, Diana Wood, Jane M. Fitzpatrick, Christine Kelly & Diwakar Jain

  2. Hospital of University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Navneet Narula, P.N. Raghunath & John E. Tomaszewski

  3. Thesius Imaging Corporation, Cambridge, Massachusetts, USA

    Neil Steinmetz & Allan Green

  4. University of Washington, Seattle, Washington, USA

    John F. Tait

  5. University of Massachusetts, Worcester, Massachusetts, USA

    Jeffrey Leppo

  6. Stanford University Medical Center, Stanford, California, USA

    Francis G. Blankenberg & H. William Strauss

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Correspondence to Jagat Narula.

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Narula, J., Acio, E., Narula, N. et al. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat Med 7, 1347–1352 (2001). https://doi.org/10.1038/nm1201-1347

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