Skip to main content Accessibility help
Hostname: page-component-77c89778f8-swr86 Total loading time: 0 Render date: 2024-07-17T17:46:46.705Z Has data issue: false hasContentIssue false

11 - Apoptosis

Published online by Cambridge University Press:  22 November 2017

Heather Jacene
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Hossein Jadvar
University of Southern California Keck School of Medicine, Los Angeles
Heather Jacene
Dana-Farber Cancer Institute, Boston
Michael Graham
University of Iowa
Get access


The Apoptosis Cellular Pathway

Apoptosis is the process of programmed cell death and is critical for growth and development and the maintenance of cellular homeostasis. Cells committed to death through the apoptotic pathway are dissembled according to a coordinated sequence of events. The classic morphologic changes during apoptosis are loss of communication and detachment from neighboring cells, condensation of chromatin at the nuclear membrane, fragmentation of the nuclear membrane, cell shrinkage, and formation of apoptotic bodies which are subsequently phagocytosed. Apoptosis is energy dependent and a distinct feature is that the cell's plasma membrane remains intact. There is no accompanying inflammatory response and no evidence of the cell's previous existence. In contrast, cellular necrosis is a disorderly process which results in surrounding inflammation and oftentimes residual tissue scarring.

Apoptosis is mediated through a number of cellular proteins and signaling pathways (Figure 11.1). The major family of proteins responsible for apoptosis is cysteine proteases called caspases. Caspases are inactivated in the cell cytoplasm (as procaspases) until receiving a death signal. Once activated, initiator caspases activate effector caspases which in turn activate the rest of the machinery needed for programmed cell death. Activation of the initiator caspases occurs via the intrinsic or mitochondrial pathway or via the extrinsic pathway.

The intrinsic (mitochondrial) pathway is induced by cellular stress or the loss of survival signals. Upon receiving such signals, mitochondria release cytochrome c through pores in the mitochondrial membrane causing apoptosome formation through oligomerization of molecules, Apaf-1 in vertebrates. Apoptosome formation results in activation of initiator caspases. The Bcl-2 family of proteins regulates the mitochondrial pathway through both anti-apoptotic (e.g., Bcl-2) and pro-apoptotic (e.g., Bak, Bax) properties.

The extrinsic pathway is activated by the binding of death ligands (e.g., tumor necrosis factor alpha) to the extracellular component of death receptors in the cell membrane. This results in the recruitment of adaptor molecules which activate initiator caspases. Subsquent formation of death receptor signaling complexes activates effector caspases leading to apoptosis. An immune response or tumorigenesis can initiate the extrinsic pathway.

Molecular Imaging
An Introduction
, pp. 47 - 51
Publisher: Cambridge University Press
Print publication year: 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Belhocine, T, Steinmetz, N, Hustinx, R, Bartsch, P, Jerusalem, G, Seidel, L, Rigo, P, Green, A. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res 2002;8:2766–2774.Google ScholarPubMed
Blankenberg, FG. In vivo detection of apoptosis. J Nucl Med 2008;49:81S–95S.CrossRefGoogle Scholar
Cohen, A, Shirvan, A, Levin, G, Grimberg, H, Reshef, A, Ziv, I. From the Gla domain to a novel small-molecule detector of apoptosis. Cell Res 2009;19:625–637.CrossRefGoogle Scholar
Saint-Hubert, M. De Bauwens, M, Verbruggen, A, Mottaghy, FM. Apoptosis imaging to monitor cancer therapy: the road to fast treatment evaluation? Current Pharmaceutical Biotechnology 2012;13:571–583.Google ScholarPubMed
Haas, RL, Jong, D de, Olmos, RA Valdés, Hoefnagel, CA, Heuvel, I van den, Zerp, SF, Bartelink, H, Verheij, M. In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys 2004;59:782–787.CrossRefGoogle ScholarPubMed
Hu, S, Kiesewetter, DO, Zhu, L, Guo, N, Gao, H, Liu, G, Hida, N, Lang, L, Niu, G, Chen, X. Longitudinal PET imaging of doxorubicin-induced cell death with (18)F-Annexin V. Mol Imaging Biol 2012 Mar 6. [Epub ahead of print].CrossRefGoogle ScholarPubMed
Kartachova, M, Zandwijk, N van, Burgers, S, Tinteren, H van, Verheij, , Olmos, RA Valdés. Prognostic significance of 99mTc-HYNIC-rh-Annexin V scintigraphy during platinum-based chemotherapy in advanced lung cancer. J Clin Oncol 2007;25:2534–2539.CrossRefGoogle Scholar
Kemerink, GJ, Liu, X, Kieffer, D, Ceyssens, S, Mortelmans, L, Verbruggen, AM, Steinmetz, ND, Vanderheyden, JL, Green, AM, Verbeke, K. Safety, biodistribution, and dosimetry of 99mTc-HYNIC-Annexin V, a novel human recombinant Annexin V for human application. J Nucl Med 2003;44:947–952.Google ScholarPubMed
Korngold, EC, Jaffer, FA, Wiessleder, R, Sosnovik, DE. Noninvasive imaging of apoptosis in cardiovascular disease. Heart Fail Rev 2008;13:163–173.CrossRefGoogle ScholarPubMed
Munõz-Pinedo, C. Signaling pathways that regulate life and cell death: evolution of apoptosis in the context of self-defense. Adv Exp Med Biol 2012;738:124–143.Google ScholarPubMed
Reshef, A, Shirvan, A, Akselrod-Ballin, A, Wall, A, ZIv, I. Small-molecule biomarkers for clinical PET imaging of apoptosis. J Nucl Med 2010;51:837–840.CrossRefGoogle Scholar
Wiele, C van de, Lahorte, C, Vermeersch, H, Loose, D, Mervillie, K, Steinmetz, ND, Vanderheyden, JL, Cuvelier, CA, Slegers, G, Dierck, RA. Quantitative tumor apoptosis imaging using technetium-99m-HYNIC-Annexin V single photon emission computed tomography. J Clin Oncol 2003;21:3483–3487.Google ScholarPubMed
Verheij, M. Clinical biomarkers and imaging for radiotherapy-induced cell death. Cancer Metastasis Rev 2008;27:471–480.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats No formats are currently available for this content.

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats No formats are currently available for this content.

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats No formats are currently available for this content.