Elsevier

Cardiology Clinics

Volume 19, Issue 1, 1 February 2001, Pages 165-172
Cardiology Clinics

NONINVASIVE STRATEGIES TO IMAGE CARDIOVASCULAR APOPTOSIS

https://doi.org/10.1016/S0733-8651(05)70202-2Get rights and content

Imaging a physiologic process usually requires a contrast material to provide a signal distinguishing the site of interest and background. In general, a target to background ratio of approximately 3:1 is required to identify the signal reliably. The process of interest can be identified by a decrease in the intensity of signal in a normal region (cold spot) or production of a signal in a region that normally has no signal (hot spot). First, the authors review the potential array of targets that can be used to identify apoptosis; second, the authors examine the history and current status of radiolabeled annexin V, the agent currently used to image apoptosis.

Apoptosis consists of a complex set of biochemical events initiated by an array of different stimuli and enzymatic pathways.2 There is a set of common morphologic and biochemical features of apoptosis that could be exploited as hot or cold spot targets to image cardiovascular apoptosis.

Section snippets

Membrane Changes in Apoptosis

Following activation of proapoptotic caspase enzymes (caspase-8 or caspase-3), the cell is committed to programmed cell death. Coincident with caspase activation there is a rapid rearrangement of the plasma membrane phospholipid structure (Fig. 1). The membrane changes result in the sudden expression of phosphatidylserine (PS), a negatively charged aminophospholipid, which normally is restricted to the inner leaflet of the lipid bilayer, on the cell surface. This is accompanied by a random

IMAGING APOPTOSIS USING RADIOLABELED ANNEXIN V

Radionuclide imaging of apoptotic cell death was initially described by Blankenberg et al6 in 1998, using radiolabeled annexin V as a hot-spot agent. Annexin belongs to a family of proteins that share the common property of calcium dependent binding to membrane bound phosphatidylserine.52 At least 20 different annexins have been identified, of which 10 have been described in mammals.49 Annexin V (MW 36.000, 319 amino acids), initially purified from human placenta,10, 51, belongs to this family

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    Address reprint requests to H. William Strauss, MD, Division of Nuclear Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Room H0101, Stanford, CA 94305, e-mail: [email protected]

    Supported in part by National Heart, Lung, and Blood Institute (NHLBI) grant number HL61717-01.

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