3PC-025 Implementation of fully automatised in-house synthesis of therapeutic radiopharmaceutical [¹⁷⁷Lu]Lu-DOTA-TOC

<h3>Background and Importance</h3> [¹⁷⁷Lu]Lu-DOTA-TOC is a beta particle-emitting radiopharmaceutical indicated for the peptide receptor radiotherapy of advanced neuroendocrine tumours (NET). The substance is characterised by affinity to somatostatin receptors, which are overexpressed in NET patients. The synthesis of this radiopharmaceutical can be performed inside specially designed isolators, manually or automatically using synthesiser and represents a challenge for every department of nuclear medicine. <h3>Aim and Objectives</h3> The aim was to implement automatised in-house synthesis of [¹⁷⁷Lu]Lu-DOTA-TOC to improve NET patient management in the department of nuclear medicine. <h3>Material and Methods</h3> Using a fully automated cassette-based synthesiser, a radiolabelling process was developed. The complexation reaction was performed in ascorbate buffer and with thermal heating of 115 µg DOTA-TOC and 8.0–8.4 GBq of ¹⁷⁷LuCl₃ solution. At the end, drug substance was eluted through sterile filter into the product vial. Then, saline was added to dilute the solution. Radiochemical purity (RCP) of [¹⁷⁷Lu]Lu-DOTA-TOC was determined by radio-HPLC and TLC. For TLC two mobile phases (0.1 M citrate buffer pH 5.5 and 1 M ammonium acetate/methanol 1:1) were used both based on ITLC-SG strips as solid phase. Confirmation of [¹⁷⁷Lu]Lu-DOTA-TOC identity was done by UV HPLC using a non-radioactive standard. In accordance with European Pharmacopoeia, sterility and endotoxine tests were performed. An automated filter integrity test was performed on the final sterile filter. <h3>Results</h3> The three validation batches of [¹⁷⁷Lu]Lu -DOTA-TOC were synthesised with an activity of 7.55 ± 0.15 GBq. The application volume was from 19 mL to 20 mL. The RCP determined by HPLC was 99.6 ± 0.5% and with TLC was 99,2 ± 0,5%. The [¹⁷⁷Lu]Lu-chloride and [¹⁷⁷Lu]Lu -colloid determined by TLC were quantified and the results obtained were 0.7, 0.14, and 0.31% for [¹⁷⁷Lu]Lu-chloride and 0.4, 0.2, and 0.4% for [¹⁷⁷Lu]Lu-colloid respectively. The retention time comparison between the standard and [¹⁷⁷Lu]Lu-DOTA-TOC was inferior to 12s. The bubble point test passed for each batch. The drug products were sterile and endotoxin-free. <h3>Conclusion and Relevance</h3> The automatised synthesis of [¹⁷⁷Lu]Lu-DOTA-TOC was successfully implemented. The reproducibility and the cost of this in-house synthesis give an opportunity to increase the access of the patients with NET to this innovative therapeutic radiopharmaceutical. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest