Speed matters to raise molar radioactivity: Fast HPLC shortens the quality control of C-11 PET-tracers.

INTRODUCTION: The decision whether an in-house produced short-lived radiopharmaceutical can be applied in-vivo is based on (1) the fulfilment of all quality criteria; (2) the availability of enough radioactivity for subsequent imaging; and (3) a molar activity (MA) above the set limits to guarantee safe administration without competing occupancy of the non-radioactive compound; and (4) an activity concentration, which is high enough for the application in certain preclinical studies. Hence, time reduction can be of major importance to increase final product yields, MA and activity concentrations. Usually, optimization in this respect only focuses on the radiotracer preparation steps but especially quality control (QC) is rarely even mentioned. Therefore, aim of this work is the establishment of optimized conditions for chromatographic analysis using HPLC within the QC to enable a significant time reduction, which then directly leads to an increase in available amount of radioactive product as well as MA at the time of application.

METHODS: An optimized set-up using ultra-performance liquid chromatography ((U)HPLC) was established and tested on 7 carbon-11 labelled radiotracers used within patient routine or clinical trials.

RESULTS: A drastic time reduction was achieved for all tracers. The optimized protocol lead to a gain of 5-7min (70-86% compared to the original set-up).

CONCLUSIONS: An accelerated (U)HPLC method for radiotracers labelled with short-lived radionuclides was successfully established and conditions were optimized for 7 clinically used radiotracers. The significant gain in QC time leads to a drastic increase in available radioactivity and specific activity at the time of tracer administration.