Two decades of [11C]PiB synthesis, 2003-2023: a review.

Because carbon-11 (11C) radiotracers cannot be shipped over long distances, their use in routine positron emission tomography (PET) studies is dependent on the production capabilities of individual radiochemistry laboratories. Since 2003, 11C-labeled Pittsburgh compound B ([11C]PiB) has been the gold standard PET radiotracer for in vivo imaging of amyloid ß (Aß) plaques. For more than two decades, researchers have been working to develop faster, higher-yielding, more robust, and optimized production methods with higher radiochemical yields for various imaging applications. This review evaluates progress in [11C]PiB radiochemistry. An introductory overview assesses how it has been applied in clinical neurologic imaging research. We examine the varying approaches reported for radiolabeling, purification, extraction, and formulation. Further considerations for QC methods, regulatory considerations, and optimizations were also discussed.

Development and Optimization of 11C-Labeled Radiotracers: A Review of the Modern Quality Control Design Process.

Introduction - Several 11C-tracers have demonstrated high potential in early diagnostic PET imaging applications of neurodegenerative diseases including Alzheimer's and Parkinson's disease. These radiotracers often track critical biomarkers in disease pathogenesis such as tau fibrils ([11C]PBB3) or ß-amyloid plaques ([11C]PiB) associated with such diseases. Purpose - The short review aims to serve as a guideline in the future development of radiotracers for students, postdocs and/or new radiochemists who will be synthesizing clinical grade or novel research 11C-tracers, including knowledge of regulatory requirements. We aim to bridge the gap between novel and established 11C-tracer quality control (QC) processes through exploring the design process and regulatory requirements for 11C-pharmaceuticals. Methods - A literature survey was undertaken to identify articles with a detailed description of the QC methodology and characterization for each of the sections of the review. Overview - First a general summary of 11C-tracer production was presented; this was used to establish possible places for contamination or assurances for a sterile final product. The key mandated QC analyses for clinical use were then discussed. Further, we assessed the QC methods used for established 11C-tracers and then reviewed the routine QC tests for preclinical translational and validation studies. Therefore, both mandated QC methods for clinical and preclinical animal studies were reviewed. Last, some examples of optimization and automation were reviewed, and implications of the QC practices associated with such procedures were considered. Conclusion - All of the common QC parameters associated with 11C-tracers under clinical and preclinical settings (along with a few exceptions) were discussed in detail. While it is important to establish standard, peer-reviewed QC testing protocols for a novel 11C-tracer entering the clinical umbrella, equal importance is needed on preclinical applications to address credibility and repeatability for the study.

Fully automated production of [11C]PiB for clinical use on Trasis-AllinOne synthesizer module.

Pittsburgh compound B ([11C]PiB) was the first broadly applied radiotracer with specificity for amyloid-ß (Aß) 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 Aß 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.