Theranostische Radiopharmaka – Translation vom Labortisch bis zur klinischen Anwendung

Abstract

This thesis addresses the development, translation, and quality assurance of theranostic radiopharmaceuticals from preclinical research to clinical application. Radiopharmacy, as a specialized field of pharmaceutical sciences, plays a pivotal role in the design and preparation of radiolabeled compounds that enable both molecular imaging and targeted radionuclide therapy. The work is divided into three main sections, reflecting the translational continuum of radiopharmaceutical research.

The first part focuses on the synthesis and characterization of novel chelating platforms for diagnostic and therapeutic radionuclides. Special attention was given to the development of heterometallic gold metallacages capable of coordinating radionuclides such as Ga-68, Lu-177 and Au-198. These complexes were evaluated for their stability, coordination behavior, and cytotoxic potential, representing a foundation for future theranostic applications with gold-based radiopharmaceuticals.

The second part of the thesis highlights the automation of radiopharmaceutical synthesis to ensure reproducible, GMP-compliant production for clinical use. Fully automated synthesis and optimization procedures were established for diagnostic tracers ([68Ga]Ga-FAPI-46 and [68Ga]Ga-PentixaFor) and therapeutic agents ([177Lu]Lu-DOTA-TOC, [177Lu]Lu-PSMA-I&T, [177Lu]Lu-FAPI-46). These developments reduced precursor consumption, increased specific activity, and enabled safe, efficient, and standardized large-scale production for multi-dose clinical application.

The third part investigates long-lived radionuclidic impurities, particularly 177mLu, which can arise during radionuclide production and pose regulatory and radioprotection challenges. The study quantified 177mLu contamination in in-house–produced and commercial radiopharmaceuticals and discussed implications for waste management and sterility testing in compliance with European and national radiation safety standards.

Overall, the thesis provides comprehensive insights into the chemical innovation, process automation, and quality control measures required to translate novel theranostic radiopharmaceuticals from the laboratory to patient care. It underscores the importance of integrating radiochemistry, pharmaceutical technology, and clinical requirements to advance personalized nuclear medicine.