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One 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 several advantages over annexin V including better pharmacokinetics due to their smaller size, better availability, simpler synthesis and radiolabeling strategies as well as facilitated tissue penetration due to their smaller size and faster blood clearance profile allowing for optimized image contrast. In addition, peptides can be structurally modified to improve metabolic stability along with other pharmacokinetic and pharmacodynamic properties. The present review will summarize the current status of radiolabeled annexins, peptides and Zn(II) complexes developed as radiotracers for imaging apoptosis through targeting PS utilizing PET and SPECT imaging. [ABSTRACT FROM AUTHOR]

Cu(I)-mediated [3+2]cycloaddition between azides and alkynes has evolved into a valuable bioconjugation tool in radiopharmaceutical chemistry. We have developed a simple, convenient and reliable radiosynthesis of 4-[F]fluoro- N-methyl- N-(propyl-2-yn-1-yl)benzenesulfonamide ( [ F]F-SA) as a novel aromatic sulfonamide-based click chemistry building block. [ F]F-SA could be prepared in a remotely controlled synthesis unit in 32 ± 5 % decay-corrected radiochemical yield in a total synthesis time of 80 min. The determined lipophilicity of [ F]F-SA (log P = 1.7) allows handling of the radiotracer in aqueous solutions. The versatility of [ F]F-SA as click chemistry building block was demonstrated by the labeling of a model peptide (phosphopeptide), protein (HSA), and oligonucleotide (L-RNA). The obtained radiochemical yields were 77 % (phosphopeptide), 55-60 % (HSA), and 25 % (L-RNA), respectively. Despite the recent emergence of a multitude of highly innovative novel bioconjugation methods for F labeling of biopolymers, Cu(I)-mediated click chemistry with [ F]F-SA represents a reliable, robust and efficient radiolabeling technique for peptides, proteins, and oligonucleotides with the short-lived positron emitter F. [ABSTRACT FROM AUTHOR]