Molar activity – The keystone in ¹¹C-radiochemistry: An explorative study using the gas phase method

Introduction: 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 ¹¹C-labeled radiotracers, the reasons for low molar activity are manifold and often the search for potential ¹²C-contaminations is time-consuming. Methods: In this study, diverse ¹²C-contaminations were analyzed and quantified, which occurred during >450 syntheses of six PET tracers using [ ¹¹C]CO ₂ or [ ¹¹C]CH ₃I generated via the gas phase method in a commercially available synthesizer. Additionally, non-radioactive syntheses were performed in order to identify the origins of carbon-12. Results: The manifold contributions to low molar activity can be attributed to three main categories, namely technical parameters (e.g. quality of target gases, reagents or tubings), inter/intralaboratory parameters (e.g. maintenance interval, burden of the module, etc.) and interoperator parameters (e.g. handling of the module). Conclusion: Our study provides a better understanding of different factors contributing to the overall carbon load of a synthesis module, which facilitates maintenance of high molar activity of carbon-11-labeled radiopharmaceuticals.