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Past, Present, and Future of Annexin A5: From Protein Discovery to Clinical Applications*

¹ Department of Nuclear Medicine, Maastricht University Hospital, Maastricht, The Netherlands
² Department of Clinical Pharmacy and Toxicology, Maastricht University Hospital, Maastricht, The Netherlands
³ Department of Cardiology, Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands
⁴ Cardiology Division, UCI Medical Center, Orange, California
⁵ Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, Maastricht, The Netherlands

In this article, we review the clinical aspects of imaging with the programmed cell–detecting protein annexin A5 (anxA5). AnxA5 binds to phosphatidylserine, which is one of the "eat me" signals at the surface of the apoptotic cell. This biologic property forms the basis for the development of anxA5 as a diagnostic tool. Within this context, the clinical relevance, limitations, and future perspectives of this approach of visualizing cell death are discussed in this article, as are other potential applications of anxA5. Furthermore, the biologic properties and the radiopharmaceutical, pharmacologic, and biodistribution aspects of anxA5 are reviewed and discussed in this article. Radiolabeled anxA5 bears the promise of becoming a clinically applied radiopharmaceutical with potential applications in cardiology and oncology. Visualization of cell death is important in pathologies such as myocardial infarction, atherosclerosis, and cancer. Furthermore, radiolabeled anxA5 may be developed as a tool for monitoring cell death–inducing or cell death–preventing therapies. In addition, experiences with radiolabeled anxA5 open novel avenues for drug targeting with anxA5 as a biologic "cruise missile."

Key Words: annexin A5 • diagnostic tool • radiopharmaceutical • clinical applications • cardiovascular disease • cancer

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