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

Introduction - Several 11 C-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 ([ 11 C]PBB3) or β-amyloid plaques ([ 11 C]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 11 C-tracers, including knowledge of regulatory requirements. We aim to bridge the gap between novel and established 11 C-tracer quality control (QC) processes through exploring the design process and regulatory requirements for 11 C-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 11 C-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 11 C-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 11 C-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 11 C-tracer entering the clinical umbrella, equal importance is needed on preclinical applications to address credibility and repeatability for the study.