[¹⁷⁷Lu]Lu-PEG-DOTA platform for theranostics: optimized radiosynthesis using domestically sourced ¹⁷⁷Lu in GA Siwabessy multipurpose reactor

This study reports the use of domestically produced ¹⁷⁷Lu for radiosynthesis and the characterization of [¹⁷⁷Lu]Lu-PEG-modified DOTA as a stable and hydrophilic precursor for targeted radiopharmaceuticals. The conjugate was synthesized by coupling DOTA-NHS ester and SH-PEG-NH₂ to form an amide, followed by radiolabeling with [¹⁷⁷Lu]LuCl₃ produced in the G.A. Siwabessy multipurpose reactor, Indonesia. Optimal labeling conditions (pH 5.0, 80°C, 1:2 molar ratio, 10 min) resulted in > 99% radiochemical purity and excellent in vitro stability in PBS (pH 7.4) for up to 168 h at 4°C and 25°C. PEGylation significantly increased the hydrophilicity, as indicated by the lower log D value (− 1.996 ± 0.028) compared to [¹⁷⁷Lu]Lu-DOTA without PEGylation (− 1.933 ± 0.057). These results indicate that DOTA modified with [¹⁷⁷Lu]Lu-PEG is a promising, stable, and highly hydrophilic platform suitable for bioconjugation with tumor-targeting biomolecules in theranostic applications. This study highlights the feasibility of utilizing locally produced ¹⁷⁷Lu for the development of advanced radiopharmaceuticals, supporting national self-reliance in nuclear medicine.