Annexin-V imaging for noninvasive detection of cardiac allograft rejection

Jagat Narula, Elmo R. Acio, Navneet Narula, Louis E. Samuels, Billy Fyfe, Diana Wood, Jane M. Fitzpatrick, P. N. Raghunath, John E. Tomaszewski, Christine Kelly, Neil Steinmetz, Allan Green, John F. Tait, Jeffrey Leppo, Francis G. Blankenberg, Diwakar Jain, H. W. Strauss

Research output: Contribution to journalArticlepeer-review

301 Scopus citations


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.

Original languageEnglish
Pages (from-to)1347-1352
Number of pages6
JournalNature Medicine
Issue number12
StatePublished - 2001
Externally publishedYes


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