Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated,

Abstract

In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2 ± 4.9%, 90.3 ± 5.6%, and 82.0 ± 8.4%, while for 177Lu-DOTATOC they were 98.3% ± 0.6, 90.8% ± 8.3, and 83.1 ± 5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15 ± 0.4 mSv/GBq, 0.04 ± 0.1 mSv/GBq, and 0.11 ± 0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02 ± 0.008 mSv/GBq, 0.01 ± 0.03 mSv/GBq, and 0.01 ± 0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb

“…Few studies, using complete automated labeling processes of peptides or antibodies with 177 Lu, have been reported to date. Syntheses investigated are mainly DOTA-based derivatives [91,92,143,171,172]. Sodium ascorbate solution is used as a buffer to adjust the reaction pH from 4.5-4.9.…”

Manual vs automated 68Ga‐radiolabelling—A comparison of optimized processes

“…The rise of gallium‐68 started with the development of somatostatin analogue edotreotide (DOTA‐TOC), which targets tumours overexpressing somatostatin receptors . Rapid accumulation in neoplastic tissue and fast clearance from healthy organs enables the delivery of a high dose of radiation on the target site and thus preserves the surrounding healthy tissue . DOTA as chelator makes it possible to apply the same molecule for diagnosis and therapy simply by the choice of radionuclide.…”

“…Nevertheless, these systems are suitable for a variety of tracers and in most cases for several radionuclides (eg, Scintomics GRP series, Eckert & Ziegler Modular‐Lab PharmTracer, and Trasis AllInOne). Additionally, the module system enhances the production process in terms of higher reliability and reduced variability …”

“…2 Rapid accumulation in neoplastic tissue and fast clearance from healthy organs enables the delivery of a high dose of radiation on the target site and thus preserves the surrounding healthy tissue. 3 DOTA as chelator makes it possible to apply the same molecule for diagnosis and therapy simply by the choice of radionuclide. This so-called theranostic approach, nowadays, well established with gallium-68/lutetium-177 as diagnostic/therapeutic pair, initiated the growing interest in radiometals for clinical application beyond technetium-99m.…”

“…Additionally, the module system enhances the production process in terms of higher reliability and reduced variability. 3,16,17 The present work focuses on the advantages of a commercial automated cassette module for the radiolabelling of bioconjugates with gallium-68 in clinical practice compared with the manual radiolabelling. Both compounds applied (DOTA-TOC and PSMA-11) were produced in our nuclear medicine frequently using a manual method, which was optimized for our site-specific needs.…”