Automated Scale-Down Development and Optimization of [68Ga]Ga-DOTA-EMP-100 for Non-Invasive PET Imaging and Targeted Radioligand Therapy of c-MET Overactivation in Cancer

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [68Ga]Ga-DOTA-EMP100 was performed using a GMP-certified 68Ge/68Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [68Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [68Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy.