Szabolcs Lehel

Alzheimer’s disease (AD) is a neurodegenerative disorder with increasing global prevalence and accounts for over half of all dementia cases. Early diagnosis is paramount for not only the management of the disease, but also for the development of new AD treatments. The current golden standard for diagnosis is performed by positron emission tomography (PET) scans with the tracer [¹¹C]Pittsburg Compound B ([¹¹C]PiB), which targets amyloid beta protein (Aβ) that builds up as plaques in the brain of AD patients. The increasing demand for AD diagnostics is in turn expected to drive an increase in [¹¹C]PiB-PET scans and the setup of new [¹¹C]PiB production lines at PET centers globally. Here, we present the [¹¹C]PiB production setups, experiences, and use from four Danish PET facilities and discuss the challenges and potential pitfalls of [¹¹C]PiB production. We report on the [¹¹C]PiB production performed with the 6-OH-BTA-0 precursor dissolved in either dry acetone or 2-butanone and by using either [¹¹C]CO₂ or [¹¹C]CH₄ as ¹¹C- precursors on three different commercial synthesis modules: TracerLab FX C Pro, ScanSys, or TracerMaker. It was found that the [¹¹C]CO₂ method gives the highest radioactive yield (1.5 to 3.2 GBq vs. 0.8 ± 0.3 GBq), while the highest molar activity (98.0 ± 61.4 GBq/μmol vs. 21.2 to 95.6 GBq/μmol) was achieved using [¹¹C]CH₄. [¹¹C]PiB production with [¹¹C]CO₂ on a TracerLab FX C Pro offered the most desirable results, with the highest yield of 3.17 ± 1.20 GBq and good molar activity of 95.6 ± 44.2 GBq/μmol. Moreover, all reported methods produced [¹¹C]PiB in quantities suitable for clinical applications, thus providing a foundation for other PET facilities seeking to establish their own [¹¹C]PiB production.

In the struggle to understand and accurately diagnose Parkinson′s disease, radiopharmaceuticals and medical imaging techniques have played a major role. By being able to image and quantify the dopamine transporter density, noninvasive diagnostic imaging has become the gold standard. In the shift from the first generation of SPECT tracers, the fluorine-18-labeled tracer [¹⁸F]FE-PE2I has emerged as the agent of choice for many physicians. However, implementing suitable synthesis for the production of [¹⁸F]FE-PE2I has proved more challenging than expected. Through a thorough analysis of the relevant factors affecting the final radiochemical yield, we were able to implement high-yielding fully automated GMP-compliant synthesis of [¹⁸F]FE-PE2I on a Synthera^®+ platform. By reaching RCYs up to 62%, it allowed us to isolate 25 GBq of the formulated product, and an optimized formulation resulted in the shelf life of 6 h, satisfying the increased demand for this radiopharmaceutical.