Apoptosis: the importance of nuclear medicine

Apoptosis is a genetically controlled, energy-dependent process which removes unwanted cells from the body. Because of its orderly progression, apoptosis is also known as programmed cell death or cell suicide. Once initiated, apoptosis is characterized by a series of biochemical and morphological changes involving the cytoplasm, nucleus and cell membrane. Cytoplasmic changes include cytoskeletal disruption, cytoplasmic shrinkage and condensation; prominent changes in the nucleus include peripheral chromatin clumping and inter-nucleosomal DNA cleavage (DNA ladder formation); and membrane changes include the expression of phosphatidylserine on the outer surface of the cell membrane and blebbing (resulting in the formation of cell membrane-bound vesicles or apoptotic bodies). These events allow the cell to digest and package itself into membrane-bound packets containing autodigested cytoplasm and DNA, which can then be easily absorbed by adjacent cells or phagocytes. An endogenous human protein, annexin V (molecular weight approximately 35,000), has an affinity of about 10(-9) M for phosphatidylserine exposed on the surface of apoptotic cells. Annexin V can be labelled with radionuclides such as iodine or technetium, or positron emitting agents. Experimental studies in cells confirm that fluorescence and 99Tc(m)-labelled annexin have comparable affinity for apoptotic cells. In vivo studies with 99Tc(m)-labelled annexin confirm that radiolabelled annexin V can be used to image apoptotic cells/tissues in vivo. In this article, we review experimental data using annexin V imaging and discuss its possible future use to identify apoptosis in vivo.