chapter  13
22 Pages

Functional Imaging of Cellular Death

WithRobert H. Mach

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).