Imaging of brain TSPO expression in a mouse model of amyotrophic lateral sclerosis with 18F-DPA-714 and micro-PET/CT

Abstract

Increased (18)F-DPA-714 uptake can be detected with high-resolution PET/CT in the brainstem of transgenic SOD1(G93A) mice, a region known to be a site of degeneration and increased microglial activation in amyotrophic lateral sclerosis, in agreement with increased TSPO expression in the brainstem nuclei shown by immunostaining. Therefore, (18)F-DPA-714 PET/CT might be a suitable tool to evaluate microglial activation in the SOD1(G93A) mouse model.

Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: Toward identification of optimal treatment windows

“…TSPO positron emission tomography (PET) is currently a reference tool for monitoring neuroinflammation involved in many brain diseases such as Alzheimer disease, stroke, traumatic brain injury, multiple sclerosis, amyotrophic lateral sclerosis, and brain tumors . There have also been studies in humans reporting increased TSPO binding in different types of epilepsy such as Rasmussen encephalitis, focal cortical dysplasia, and mesial temporal lobe epilepsy (MTLE) .…”

A concisely automated synthesis of TSPO radiotracer [18F]FDPA based on spirocyclic iodonium ylide method and validation for human use

“…The half-life was verified to be 110.9 minutes by a dose calibrator. No long-lived isotopes were observed (7 days), as determined by the analysis on a HPGE detector after 18 F-decay. The masses in the formulated solution were determined from a standardized curve, which were used for the calculation of molar activities (529.2 ± 22.5 GBq/ μmol, 14.3 ± 0.6 Ci/μmol).…”

“…1. 18 preloaded into Vial 3 was added to REACTOR 1. The reactor was sealed via the closure of valves V13, V20, and V24, and the reaction mixture was heated to 120 C for 15 minutes.…”

“…As a result, next‐generation TSPO radiotracers have been developed recently to overcome the limitations of [ 11 C]PK11195. Among these, [ 18 F]DPA‐714 ( K i = 7.0 ± 0.4 nM) showed excellent PET imaging profile due to the lower nonspecific binding and higher signal‐to‐noise ratio as compared with [ 11 C]PK11195, and has been translated to clinical studies for evaluation of AD and amyotrophic lateral sclerosis . However, the fluoro‐ethoxyl functionality resulted in the formation of [ 18 F]‐labeled small metabolites such as [ 18 F]deethyl, [ 18 F]hydroxyl, and [ 18 F]carboxylic acid derivatives, which would compromise the imaging performance and further quantification …”

“…Among these, [ 18 F]DPA-714 [10][11][12][13][14][15][16] (K i = 7.0 ± 0.4 nM) showed excellent PET imaging profile due to the lower nonspecific binding and higher signal-to-noise ratio as compared with [ 11 C]PK11195, 17 and has been translated to clinical studies for evaluation of AD 15 and amyotrophic lateral sclerosis. 18 19 [ 18 F]FDPA, an analog of [ 18 F]DPA-714, showed excellent binding affinity for TSPO (Ki = 2.0 ± 0.8 nM using the same [ 3 H]PK11195 binding assay and positive controls described in the DPA-714 work), 11 excellent selectivity toward central benzodiazepine receptor (Ki > 1 mM), and reasonable lipophilicity (LogD = 2.34) for crossing blood-brain barrier. 20,21 More importantly, its aryl-18 F bond significantly reduced the potential generation of radiolabeled metabolites in the brain and plasma, 22 which would help PET quantification.…”