technical-aspect-automated-synthesis-real-time-kinetic-evaluation

Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [<sup>11</sup>C]SNAP-7941

Positron emission tomography (PET) is an essential molecular imaging technique providing insights into pathways and using specific targeted radioligands ...

Medical University of Vienna

Radiosynthetic optimization is crucial in routine PET production but is often neglected in literature. Small changes in the radiochemical procedure can increase the yield significantly and reduce time fluctuation within the synthetic procedure enabling better planning and product release on time. Therefore, a highly reproducible production method for L-[S-methyl-C]methionine is presented, which uses a fully automated GE TRACERlab FX C Pro synthesizer. Evolution of the synthetic procedure lead to a protocol with a nearly doubled absolute yield.

L-[S-methyl-C]methionine - An example of radiosynthetic optimization.

Radiochemists/radiopharmacists, involved in the preparation of radiopharmaceuticals are regularly confronted with the requirement of continuous high quality productions in their day-to-day business. One of these requirements is high specific or molar activity of the radiotracer in order to avoid e.g. receptor saturation and pharmacological or even toxic effects of the applied tracer for positron emission tomography. In the case of C-labeled radiotracers, the reasons for low molar activity are manifold and often the search for potential C-contaminations is time-consuming.

Molar activity - The keystone in C-radiochemistry: An explorative study using the gas phase method.

The tracer -Hydroxyephedrine ([[11C]HED) is one of the most applied PET tracers for cardiac imaging, whose radiosynthesis was already reported in 1990. While not stated in the literature, separation difficulties and an adequate formulation of the product are well known challenges in its production. Furthermore, the precursor (metaraminol) is also a substrate for the norepinephrine transporter, and can therefore affect the image quality. This study aims at optimizing the synthetic process of [[11C]HED and investigating the effect of the apparent molar activity (sum of HED and metaraminol) in patients and animals. The main optimization was the improved separation through reverse phase-HPLC by a step gradient and subsequent retention of the product on a weakly-cationic ion exchange cartridge. The µPET/µCT was conducted in ten rats (ischemic model) and the apparent molar activity was correlated to the VOI- and SUV-ratio of the myocardium/intra-ventricular blood pool. Moreover, nine long-term heart transplanted and five Morbus Fabry patients underwent PET and MRI imaging for detection of changes in the sympathetic innervation. In summary, the fully-automated synthesis and optimized purification method of [[11C]HED is easily applicable and reproducible. Moreover, it was shown that the administered apparent molar activities had a negligible effect on the imaging quality.

Article	Year
L-[S-methyl-C]methionine - An example of radiosynthetic optimization. Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine\| PubMed ID: 30196247	2018
Molar activity - The keystone in C-radiochemistry: An explorative study using the gas phase method. Nuclear medicine and biology\| PubMed ID: 30380463	2018
Optimization of the Automated Synthesis of [11C]mHED-Administered and Apparent Molar Activities. Pharmaceuticals (Basel, Switzerland)\| PubMed ID: 30646635	2019

Verena Pichler

Biography

JoVE Journal Publications

Other Publications