DOI: https://doi.org/10.2478/acph-260013
Article ID: 260013 (16 pages)
Acta Pharm. 76(2) (2026)
Article
Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical
PAULINA APOSTOLOVA, MARIJA ATANASOVA LAZAREVA, KATARINA DAVALIEVA, MARIJA AREV, DINO KARPICAROV, PETRE MAKRESKI, IRENA SLAVESKA SPIREVSKA, IVANA MITREVSKA, ALEKSANDAR DIMOVSKI, SANJA VRANJEŠ-ĐURIĆ, EMILIJA JANEVIK-IVANOVSKA
Abstract
Daratumumab is a fully human anti-CD38 monoclonal antibody with strong potential as a targeting vector for therapeutic radionuclides. This study aimed to develop a freeze-dried daratumumab immunoconjugate kit by selecting a suitable chelator (DOTA-NHS, p-SCN-Bn-DOTA, or p-SCN-Bn-1B4M-DTPA) for the 177Lu-labelling, optimising the freeze-drying formulation, and evaluating the physicochemical properties and purity profiles. Conjugation performed in carbonate buffer at elevated temperature enhanced chelator incorporation and supported the selection of daratumumab-p-SCN-Bn-DOTA as the most suitable candidate, achieving radiolabelling yield up to 99.8 % without additional purification. Among the evaluated freeze-dried formulations, a saline-based, buffer-free sucrose-mannitol formulation containing polysorbate 20 (S.F5) provided the most favourable characteristics, including minimal residual moisture and the highest monomer purity with non-detectable HMWS species under the applied SE-HPLC conditions. ATR-FTIR and Raman spectroscopy confirmed preservation of the antibody structural integrity after conjugation and freeze-drying. In an in vitro study using human serum, [177Lu]Lu-daratumumab-p-SCN-Bn-DOTA maintained higher radiochemical purity for 168 h than [177Lu]Lu-daratumumab-p-SCN-Bn-1B4M-DTPA, indicating greater stability. These results support the feasibility of a ready-to-use freeze-dried daratumumab-p-SCN-Bn-DOTA kit for the 177Lu-labelling.
Keywords
daratumumab, immunoconjugate, 177Lu-radiopharmaceutical, ready-to-use kit formulation, freeze-drying, physicochemical characterization
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