Challenges in Production of Alzheimer’s Tracer C-11 PiB

Multicenter Experience with Good Manufacturing Practice Production of [11C]PiB for Amyloid Positron Emission Tomography Imaging

“…The purification of [ 11 C]PiB from the crude reaction mixture into the final product formulation was performed at all sites using semi-preparative HPLC. The separation procedures were also performed with similar parameters ( Table 2 ) and were based on in-house experiences and from the literature [ 5 , 13 , 14 , 15 , 21 ]. The main differences between these procedures are the choice of HPLC column (manufacturer and dimensions) and the ratio between the aqueous and non-aqueous (ethanol) eluent.…”

“…The short t ½ for 11 C also poses a challenge for the separation and formulation of [ 11 C]PiB from the reaction mixture, where fast purification is desirable. Here, the most common strategy has been semi-preparative high performance liquid chromatography (HPLC) [5,[13][14][15]20,21], where compound separation is performed by larger HPLC columns and faster flowrates compared to analytical HPLC methods. Various semi-preparative HPLC setups (columns, eluents, and flowrates) have been reported but all with general retention times of less than 10 min; however, in some cases, an additional purification step of the product fraction is performed by elution through commercially available singleuse chromatographic cartridges [20,21].…”

“…AD is the most prevalent form of dementia and is characterized by the accumulation of amyloid beta protein (Aβ) as plaques in the brain and acts as the biological target for [ 11 C]PiB [2]. The accumulation of Aβ may begin up to two decades before the patient displays AD symptoms and is detectable by PET [2][3][4][5]; thus, [ 11 C]PiB-PET is a powerful tool for the differentiation of dementia types, early detection of AD, and assessment of tool for the differentiation of dementia types, early detection of AD, and assessment of new AD treatments. Recently, immunotherapies that target Aβ have been approved by the FDA, and more candidate drugs are in clinical trials [6].…”

Amyloid PET Radiopharmaceuticals and Imaging for Clinical and Research Applications in Thailand

“…The Wattanosoth Hospital in Bangkok was the first center in Thailand to start developing [ 11 C]PIB in November, 2012. 45 The National Cyclotron and PET Centre at the Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, started producing [ 11 C]PIB in 2017 46 45 The current [ 11 C]PiB production at Wattanosoth Hospital can service 2-3 dementia patients a day requiring amyloid PET scan for an early diagnosis to allow a better chance of benefiting from treatment, participating in clinical drug trials, and allowing more time to plan for the future. Nevertheless, to our knowledge, there has been no available published data on clinical performance of [ 11 C]PiB PET scan.…”