Procedures for GMP-Compliant Production of [¹⁷⁷Lu]Lu-PSMA-I&T, Quality Control, and Evaluation of Stability Over Five Days

¹Arsyangela Verena, ¹Fan-Chieh Meng, ¹Chi-Wei Chang, ¹Ya-Ting Huang, ¹Ya-Yao Huang*

¹R&D Department, Primo Biotechnology Co., Ltd., Taipei, Taiwan

Introductions:

[¹⁷⁷Lu]Lu-PSMA-I&T is an FDA-approved, clinically validated ligand for radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), with encouraging clinical results reported in multiple studies. To support reliable clinical translation and potential large-scale production in Taiwan, a robust GMP-compliant automated synthesis and quality control (QC) process are required. We report procedures for the GMP-compliant production of [¹⁷⁷Lu]Lu-PSMA-I&T using the iPHASE MultiSyn synthesizer. Quality control was performed according to the European Pharmacopoeia monograph (EP 11.7), and an extended stability study was conducted over five days in a GMP- compliant facility.

Methods:

The DOTAGA-PSMA-I&T precursor was obtained from ABX (Radeberg, Germany). Sodium acetate buffer, sodium L- ascorbate, and gentisic acid were from Huayi Isotopes Co., and NCA [¹⁷⁷Lu]LuCl₃ was obtained from SHINE Technologies (Janesville, US). Automated radiosynthesis of [¹⁷⁷Lu]Lu-PSMA-I&T was performed on an iPHASE MultiSyn synthesizer. The precursor was dissolved in 0.3 M sodium acetate buffer (pH 5.0) with gentisic acid and radiolabeled with [¹⁷⁷Lu]LuCl₃ at 95°C for 18 min. The crude reaction mixture was diluted with 10 mL sodium ascorbate/DTPA solution and filtered through a 0.22-µm Millex filter into the final product vial.Quality control was performed according to EP 11.7. Radiochemical purity (RCP) was determined by HPLC (Waters e2695) using a Kinetex 5 µm C18 150 × 4.6 mm column. The mobile phase consisted of solvent A (25.7 mM NaH₂PO₄, pH 2.5 ± 0.1) and solvent B (acetonitrile). A multi-step gradient was applied: 0–2 min, 80% A; 2–10 min, linear to 75% A; 10–12 min, linear to 40% A; 12–14 min, hold at 40% A; 14–14.5 min, linear to 80% A; 14.5-22 min hold at 80% A. The flow rate was 1.0 mL/min, with a total run time of 22 min. Retention times of the reference standard and product were 7.021 and 7.186 min, respectively. RCP was evaluated by TLC on NP iTLC silica gel plates, developed with citrate buffer (pH 5.0) and dried, and scanned using a radio-TLC analyzer (Scan-Ram, Lablogic). Stability was assessed at room temperature over 5 days, with daily RCP evaluation.

Results and Discussions:

[¹⁷⁷Lu]Lu-PSMA-I&T was obtained in 44 min with a final pH of 5.5, a radiochemical yield >80%, radiochemical purity >95%, and radionuclidic purity >99.9%. All content of impurities met the acceptance criteria specified in the EP. The final product was sterile, pyrogen-free, and stable at room temperature, with an RCP greater than 95% maintained for up to five days.

Conclusions:

We established a GMP-compliant, fully automated radiosynthesis of [¹⁷⁷Lu]Lu-PSMA-I&T using the iPHASE MultiSyn synthesizer, producing a final product that met all EP quality specifications and remained stable for at least 5 days at room temperature. These results support the feasibility of routine GMP production and large-scale clinical application of [¹⁷⁷Lu]Lu-PSMA-I&T in Taiwan.