Heart transplant rejection is characterized pathologically by myocyte necro
sis and apoptosis associated with interstitial! mononuclear cell infiltrati
on. 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 membra
ne bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogen
ous protein that has high affinity for binding to phosphatidylserine, has b
een administered intravenously for noninvasive identification of apoptotic
cell death. In the present study of 18 cardiac allograft recipients, 13 pat
ients had negative and five had positive myocardial uptake of annexin. Thes
e latter five demonstrated at least moderate transplant rejection and caspa
se-3 staining, suggesting apoptosis in their biopsy specimens. This study r
eveals the clinical feasibility and safety of annexin-V imaging for noninva
sive detection of transplant rejection by targeting cell membrane phospholi
pid alterations that are commonly associated with the process of apoptosis.