DOI: https://doi.org/10.2478/acph-260013
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 177Lu-labeling, optimizing 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 selection of daratumumab–p-SCN-Bn-DOTA as the most suitable candidate, achieving radiolabeling 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 favorable 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 was shown to maintain higher radiochemical purity over 168 h compared to [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 177Lu-labeling.
Keywords
daratumumab, immunoconjugate, 177Lu-radiopharmaceutical, ready-to-use kit formulation, freeze-drying, physicochemical characterization
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