Subject: Other medical sciences
Year: 2026
Type: Article
Type: PeerReviewed
Title: Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical
Author: Apostolova, Paulina
Author: Atanasova Lazareva, Marija
Author: Davalieva, Katarina
Author: Arev, Marija
Author: Karpicarov, Dino
Author: Makreski, Petre
Author: Slaveska Spirevska, Irena
Author: Mitrevska, Ivana
Author: Dimovski, Aleksandar
Author: Vranjes-Djuric, Sanja
Author: Janevik-Ivanovska, Emilija
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 nondetectable 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-SCNBn- DOTA maintained higher radiochemical purity for 168 h than [177Lu]Lu-daratumumab-p-SCN-Bn-1B4MDTPA, 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.
Publisher: Croatian Pharmaceutical Society
Relation: https://eprints.ugd.edu.mk/38440/
Identifier: oai:eprints.ugd.edu.mk:38440
Identifier: https://eprints.ugd.edu.mk/38440/1/Freeze-dried%20kit%20formulation%20and%20physicochemical%20assessment%20of.pdfIdentifier: Apostolova, Paulina and Atanasova Lazareva, Marija and Davalieva, Katarina and Arev, Marija and Karpicarov, Dino and Makreski, Petre and Slaveska Spirevska, Irena and Mitrevska, Ivana and Dimovski, Aleksandar and Vranjes-Djuric, Sanja and Janevik-Ivanovska, Emilija (2026) Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical. Acta Pharmaceutica, 76 (2). ISSN 1330-0075
