18 F-labelled annexin V: a PET tracer for apoptosis imaging

Abstract

Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [18F]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [18F]annexin V was synthesised using N-succinimidyl 4-[18F]fluorobenzoate as an 18F labelling reagent. Synthesised and purified [18F]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [18F]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [18F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [18F]annexin V or [(99m)Tc]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [18F]annexin V and [(99m)Tc]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [18F]annexin V in the liver, spleen and kidney was much lower than that of [(99m)Tc]annexin V. The low uptake of [18F]annexin V in these organs might represent an advantage over [(99m)Tc]annexin V.

In vivo imaging of apoptosis

“…The adverse effects of heating annexin V can be seen with the pre-formed chelate approach, in which 99m Tc is sequestered by reacting with succinic dihydrazide (SDH) along with tricine and nicotinic acid, followed by conjugation to the annexin V by heating at 90°C as proposed by Subbarayan et al 65 As compared with SPECT PET has major advantages for quantitative imaging, and has spurred the development of several approaches to label annexin V with fluorine 18 ( 18 F). 66,67 One method has used N-succinimidyl 4-fluorobenzoate to synthesize 18 F-annexin V. The fluorine labeled agent has lower uptake in the liver, spleen and kidney compared to HYNIC-annexin V. Another method involves site-specific derivatization with an 18 F-maleimide labeled compound to mutant annexin V-117 or annexin V-128. 68 Both these methods however need more preclinical study before further development as imaging markers of apoptosis.…”

PET/CT imaging in cancer: Current applications and future directions

“…More recently, 18 F-annexin V has been synthesized, and it has an improved biodistribution profile and can be imaged using PET; preliminary studies of 18 F-annexin V have been done in animals but not in humans. 96 A second class of imaging agents targets caspases, which are cysteine-aspartate proteases that play a pivotal role in the regulation of apoptosis. Two of the main imaging agents in this class are 18 F-ICMT-11 (a caspase-3-specific small molecule PET tracer based on the caspase inhibitor isatin) and 18 F-CP18 (a pentapeptide-based PET tracer that is a substrate of caspase-3).…”

Current Molecular Imaging Positron Emitting Radiotracers in Oncology

“…18 F-labeled annexin V is a PET tracer for apoptosis imaging through labeling of wild-type annexin V with N-succinimidyl-4-18 F-fluorobenzoate [108]. 18 F-labeled annexin V was applied to evaluate myocardial ischemia in a rat model, and accumulation in the left ventricle was examined [109]. Rat liver apoptosis induced by cycloheximide was evaluated by 18 F-labeled annexin V and resulted in a 3-to 9-fold increase in uptake of 18 F-annexin V in the liver apoptosis group at 2 h, compared with controls, which is consistent with histological analysis [110].…”