Abstract
A novel annexin V derivative (Cys-Annexin V) with a single cysteine residue at its C-terminal has been successfully labeled site-specifically with NOTA-maleimide aluminum [18F]fluoride complexation and evaluated it as a novel apoptosis agent in vitro and in vivo. The total synthesis time of 18F-AlF-NOTA-MAL-Cys-Annexin V from [18F]fluoride was about 65 min. The tracer was stable in vitro and it was excreted through renal in normal mice. The rate of the tracer bound to erythrocytes with exposed phosphatidylserine was 89.36±0.61% and this binding could be blocked by unlabeled Cys-Annexin V. In rats treated with cycloheximide, there were 6.23±0.23 times (n=4) increase in hepatic uptake of the tracer as compared to normal rats at 1h p.i. The uptake of the tracer in liver also could be blocked by co-injection of unlabeled Cys-Annexin V. These results indicated the favorable characterizations such as convenient synthesis and specific apoptotic cells targeting of18F-AlF-NOTA-MAL- Cys-Annexin V were suitable for its further investigation in clinical apoptosis imaging.
Highlights
Apoptosis, known as programmed cell death, is an important way to maintain the relative balance of the body, which is closely related with a variety of pathological processes such as myocardial ischemia and tumor response to treatment [1, 2]
The uptake of the tracer in liver could be blocked by co-injection of unlabeled Cys-Annexin V. These results indicated the favorable characterizations such as convenient synthesis and specific apoptotic cells targeting of18F-AlF-NOTA-MALCys-Annexin V were suitable for its further investigation in clinical apoptosis imaging
Annexin V labeled with various radionuclides are useful as radiotracers in vivo imaging of apoptosis as single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging agents
Summary
Known as programmed cell death, is an important way to maintain the relative balance of the body, which is closely related with a variety of pathological processes such as myocardial ischemia and tumor response to treatment [1, 2]. During the early phase of apoptosis, phosphatidylserine (PS) in the lipid bilayer of the cell membrane is flipped from the inner layer to the outer layer and exposed to the cell surface [3, 4]. It is a good target for the development of probe to image apoptotic cells [5]. Annexin V with high-affinity for PS is an endogenous protein with a molecular weight of about 36-kD and contains about 319 amino acids It belongs to the calcium-dependent phospholipid-binding protein family and always used as PS targeting agent [6, 7]. In a wide array of preclinical [11, 13] and clinical studies [14,15,16]99mTc-HYNIC-Annexin V imaging was useful to assess tumor response to therapy
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