Pittsburgh Compound B

Positron emission tomography (PET) probes are specific and sensitive while suffering from radiation risk. It is worthwhile to explore the chemical emission saturation transfer (CEST) effects of the probe prototypes and repurpose them for CEST imaging to avoid radiation. In this study, we used ¹¹C-PiB as an example of a PET probe for detecting amyloid and tested the feasibility of repurposing this PET probe prototype, PiB, for CEST imaging. After optimizing the parameters through preliminary phantom experiments, we used APP/PS1 transgenic mice and age-matched C57 mice for in vivo CEST magnetic resonance imaging (MRI) of amyloid. Furthermore, the pathological assessment was conducted on the same brain slices to evaluate the correlation between the CEST MRI signal abnormality and β-amyloid deposition detected by immunohistochemical staining. In our results, the Z-spectra revealed an apparent CEST effect that peaked at approximately 6 ppm. APP/PS1 mice as young as 9 months injected with PiB showed a significantly higher CEST effect compared to the control groups. The hyperintense region was correlated with the Aβ deposition shown by pathological staining. In conclusion, repurposing the PET probe prototype for CEST MRI imaging is feasible and enables label- and radiation-free detection of the amyloid while maintaining the sensitivity and specificity of the ligand. This study opens the door to developing CEST probes based on PET probe prototypes.

Pittsburgh compound B ([¹¹C]PiB) was the first broadly applied radiotracer with specificity for amyloid-β (Aβ) peptide aggregates in the brain and has since been established as the gold standard for positron emission tomography (PET) employed for clinical in vivo imaging of Aβ plaques, used for imaging applications of Alzheimer's disease (AD), related dementia, and other tauopathies. The use of [¹¹C]PiB for routine PET studies is dependent on the production capabilities of each radiochemistry laboratory, subsequently a continuous effort is made to develop suitable and sustainable methods on a variety of auto synthesis platforms. Here we report a fully automated, multi-step radio synthesis, purification, and reformulation of [¹¹C]PiB for PET imaging using the Trasis AllinOne synthesis unit, a commonly used commercial radiochemistry module. We performed three validation runs to evaluate the reproducibility and to verify that the acceptable criteria were met for the release of clinical-grade [¹¹C]PiB using a Trasis AllinOne auto radiosynthesis unit. Solid phase supported radiolabeling was performed through the capture of precursor (6-OH-BTA-0) on a C18 solid phase extraction (SPE) cartridge and subsequent flushing of gaseous [¹¹C]Methyl triflate(MeOTf) through the Sep-Pak for carbon-11 (¹¹C) N-methylation. Starting with 92.5 GBq [¹¹C]CO₂, [¹¹C]PiB synthesis was completed in approximately 25 min after cyclotron end of bombardment with an injectable dose >7.0 GBq at end of the synthesis. The radiopharmaceutical product met all quality control criteria and specifications for use in human studies.