Automated GMP Production and Preclinical Evaluation of [⁶⁸Ga]Ga-TEoS-DAZA and [⁶⁸Ga]Ga-TMoS-DAZA

• Main Authors: Julia Greiser (Author), Thomas Winkens (Author), Olga Perkas (Author), Christian Kuehnel (Author), Wolfgang Weigand (Author), Martin Freesmeyer (Author)
• Format: Book
• Published: MDPI AG, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14122695; 1999-4923
• Keywords: Gallium-68; PET; radiopharmacy; liver diagnostics; imaging; N,O ligands; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 12, p 2695 (2022)

[⁶⁸Ga]Ga-TEoS-DAZA and [⁶⁸Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the ⁶⁸Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [⁶⁸Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [⁶⁸Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [⁶⁸Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [⁶⁸Ga]Ga-TEoS-DAZA and [⁶⁸Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible.