Semi-automatic synthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc (II)-dipicolylamine) (18F-FP-DPAZn2) for AD model imaging

Abstract

BackgroundPhosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (18F-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer’s disease (AD) model, were performed.Methods 18F-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was determined in normal mice and PET images of AD model were obtained on a micro PET-CT scanner.ResultsWith the modified synthesizer, the total decay-corrected radiochemical yield of 18F-FP-DPAZn2 was 35 ± 6% (n = 5) from 18F− within 105 ± 10 min. Biodistribution results showed that kidney has the highest uptake of 18F-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low level during the whole observed time. In vivo 18F-FP-DPAZn2 PET images demonstrated more accumulation of radioactivity in the brain of AD model mice than that in the brain of normal mice.ConclusionsThe semi-automatic synthetic method provides a slightly higher radiochemical yield and shorter whole synthesis time of 18F-FP-DPAZn2 than the manual operation method. This improved method can give enough radioactivity and high radiochemical purity of 18F-FP-DPAZn2 for in vivo PET imaging. The results show that 18F-FP-DPAZn2 seems to be a potential cell death tracer for AD imaging.

Imaging Cell Death: Focus on Early Evaluation of Tumor Response to Therapy

“…This was consistent with previous research, which showed that the low absolute uptake of two 99m Tc-labeled Zn 2+ -DPA coordination complexes in the injured myocardium might be less detectable by SPECT imaging . Overall, both the PET and SPECT probes based on Zn 2+ -DPA complexes showed low to moderate uptake in the target tissues and high uptake in the abdomen. − Therefore, further structural modification to enhance PS-binding affinities of Zn 2+ -DPA-based molecular probes as well as to improve their pharmacokinetic properties is essential for improving in vivo imaging performance.…”

“…In contrast, 18 F-FDG exhibited no significant change in tumor uptake between doxorubicin-treated mice and untreated mice . The same research group subsequently prepared a structurally similar probe named 18 F-FP-DPAZn2 and developed a semiautomatic synthetic method. , The potential of 18 F-FP-DPAZn2 for imaging apoptosis was confirmed in rats with acute myocardial infarction and in mice with Alzheimer’s disease. , However, whether this probe can be used for imaging of tumor apoptosis following anticancer treatment has not been investigated.…”

Imaging the Bacterial Cell Wall Using N-Acetyl Muramic Acid-Derived Positron Emission Tomography Radiotracers

“…Fujiwara et al described the analogous N -[ 18 F]­fluoroacetyl- d -glucosamine with imaging in a murine tumor model showing moderate bone uptake . We therefore decided to acylate muramic acid with 4-nitrophenyl 2-[ 18 F]­fluoropropionate ([ 18 F]­NFP), , to validate the NAM-derived diastereomers ( S )-[ 18 F]­FMA and ( R )-[ 18 F]­FMA for imaging bacterial infection. Successful use of N -acylation for NAM radiolabeling would also motivate new methods for 18 F-incorporation into NAc mimics that can be applied to various metabolites of biochemical/medicinal interest.…”