ABSTRACT
I. Introduction 327
II. Apoptosis vs. Necrosis 328
III. The Need to Discriminate Between Apoptosis and Necrosis 331
IV. Measurement of Apoptosis and Necrosis In Vitro 333
V. Measurement of Apoptosis and Necrosis In Vivo Using
Functional Imaging Techniques 335
A. Radiolabeled Annexin V Analogs 336
B. Imaging Agents Based on Caspase-3 340
C. Imaging PARP-1 Activity in Cells Undergoing Necrosis 342
VI. Imaging Cell Death During Lung Health and Disease 343
VII. Conclusion 345
Acknowledgments 345
References 345
I. Introduction
Apoptosis is a tightly regulated mode of cellular death that does not result in
injury to neighboring cells or elicit an inflammatory response. On the other
hand, necrosis is a catastrophic, unregulated mode of cell death that is followed
by the invasion of inflammatory cells (1). Although apoptosis and necrosis are
caused by distinct biochemical pathways, there is a great deal of experimental
evidence to suggest that both processes are observed in diseases characterized by
abnormal cellular death. Although there are a number of factors that can induce
cell death, both apoptosis and necrosis are often the end result of the exposure of
normal tissue to oxidative stress. When this occurs, the balance between the
amount of tissue undergoing apoptosis and necrosis is dependent on a variety
of factors including the severity of the oxidative stress. The development of non-
invasive imaging procedures for measuring apoptosis and necrosis could provide
valuable information regarding the relative contribution of each in tissues under-
going abnormal cellular death. This chapter will provide a review of noninvasive
imaging procedures for imaging cellular death in vivo. Procedures that are cur-
rently being used in human imaging studies as well as newer strategies currently
under development will be presented. A description of the use of the imaging
agents, 99mTc-pyrophophate and 111In-antimyosin, for imaging necrosis in myo-
cardial infarction will not be presented but can be found in the recent review by
Flotats and Carrio (2).
