Targeting phosphatidylserine for radionuclide-based molecular imaging of apoptosis

AbstractOne major characteristic of programmed cell death (apoptosis) results in the increased expression of phosphatidylserine (PS) on the outer membrane of dying cells. Consequently, PS represents an excellent target for non-invasive imaging of apoptosis by single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Annexin V is a 36  kDa protein which binds with high affinity to PS in the presence of Ca2+ ions. This makes radiolabeled annexins valuable apoptosis imaging agents for clinical and biomedical research applications for monitoring apoptosis in vivo. However, the use of radiolabeled annexin V for in vivo imaging of cell death has been met with a variety of challenges which have prevented its translation into the clinic. These difficulties include: complicated and time-consuming radiolabeling procedures, sub-optimal biodistribution, inadequate pharmacokinetics leading to poor tumour-to-blood contrast ratios, reliance upon Ca2+ concentrations in vivo, low tumor tissue penetration, and an incomplete understanding of what constitutes the best imaging protocol following induction of apoptosis. Therefore, new concepts and improved strategies for the development of PS-binding radiotracers are needed. Radiolabeled PS-binding peptides and various Zn(II) complexes as phosphate chemosensors offer an innovative strategy for radionuclide-based molecular imaging of apoptosis with PET and SPECT. Radiolabeled peptides and Zn(II) complexes provide s...

Source: Apoptosis - January 25, 2019 Category: Molecular Biology Source Type: research