Synthesis and In Vitro and In Vivo Evaluation of ¹⁸F-Labeled Positron Emission Tomography Tracers for Imaging Aβ Plaques

Abstract

Accurate quantification of amyloid beta (Aβ) plaques is an important indicator for Alzheimer’s disease diagnosis and treatment. For this purpose, new highly sensitive Aβ tracers were designed by regulating the position and number of nitrogen atoms. A series of derivatives of florbetapir (AV45) containing different numbers and positions of N atoms were synthesized and evaluated for in vitro affinity and in vivo biodistribution. Preliminary study results showed that [18F]­BIBD-124 and [18F]­BIBD-127 had better clearance rates and less in vivo defluorination than AV45 in ICR (ICR = Institute of Cancer Research) mice. Autoradiography and molecular docking indicated that the binding sites of [18F]­BIBD-124/127 were similar to that of [18F]­AV45. Micro-positron emission tomography-computed tomography imaging further demonstrated that [18F]­BIBD-124 could monitor Aβ plaques similar to [18F]­AV45. Besides, the imaging contrast of [18F]­BIBD-124 is better than that of [18F]­AV45. Mass spectrometric metabolic analysis showed that BIBD-124 was less demethylated than AV45 without subsequent acetylation, which might explain its less non-specific uptake and higher imaging contrast. Gauss calculations further confirmed that the introduction of N5 in [18F]­BIBD-124 decreased demethylation. Considering imaging contrast and in vivo defluorination, [18F]­BIBD-124 is expected to be a promising radiotracer of Aβ plaques for further clinical trials.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1

“…Nude mice (female, weight 12–16 g) bearing MCF-7 and 22Rv1 xenografts and intracranial U87MG and C6 tumors were purchased from Guangdong GemPharmatech Co., Ltd. Data were recorded on a Madiclab PSA146 PET/CT/FMT instrument. Dynamic microPET-CT imaging studies were conducted with [ 18 F]­8a , [ 18 F]­8d , [ 18 F]­8g , [ 18 F]­8j , [ 18 F]­FTT, or [ 18 F]­BIBD-300, similar to that reported previously . A total of 8–11 MBq of activity was injected intravenously via the lateral tail vein.…”

“…[ 18 F]FTT, or [18 F]BIBD-300, similar to that reported previously 28. A total of 8−11 MBq of activity was injected intravenously via the lateral tail vein.…”

Design, Synthesis, and Evaluation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein for Brain Imaging

“…Nude mice (female, weight 12–16 g) bearing U87MG xenografts and intracranial tumors were purchased from Guangdong GemPharmatech Co., Ltd. Data were recorded on a Madiclab PSA146 PET/CT/FMT instrument. Dynamic microPET-CT imaging studies were conducted with [ 18 F]­1a , [ 18 F]­1b , or [ 68 Ga]­FAPI04, similar to that reported previously . A total of 8–11 MBq of activity was injected intravenously via the lateral tail vein.…”

“…Dynamic microPET-CT imaging studies were conducted with [ 18 F]1a, [ 18 F]1b, or [ 68 Ga]FAPI04, similar to that reported previously. 29 imaging was collected at 2 and 4 h postinjection. All animals were sedated with isoflurane anesthesia (2−3%, 1 L/min oxygen) and then placed on a heating pad to maintain body temperature throughout the procedure.…”

Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging

“…Data were recorded on a Madiclab PSA146 PET/CT/FMT instrument. Dynamic small animal PET-CT imaging studies were conducted with (2S,4S)-4-[ 18 F]­FEBGln similar to that reported previously. , All scans were performed on a dedicated animal PET scanner. Nude mice with MCF-7, NCI-h1975, 22Rv1, or U87MG tumors were used for the imaging studies.…”