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

doi:10.2478/acph-2026-0013

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Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical

Acta Pharmaceutica

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By: Paulina Apostolova , Marija Atanasova Lazareva , Katarina Davalieva , Marija Arev , Dino Karpicarov , Petre Makreski , Irena Slaveska Spirevska , Ivana Mitrevska , Aleksandar Dimovski , Sanja Vranješ-Đurić and Emilija Janevik-Ivanovska

Open Access

|May 2026

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-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.

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Articles in this issue

DOI: https://doi.org/10.2478/acph-2026-0013 | Journal eISSN: 1846-9558 | Journal ISSN: 1330-0075

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Language: English

Accepted on: May 4, 2026

Published on: May 27, 2026

Published by: Croatian Pharmaceutical Society

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

daratumumab,

immunoconjugate,

¹⁷⁷Lu-radio-pharmaceutical,

ready-to-use kit formulation,

freeze--drying,

physicochemical characterization

Related subjects:

Pharmacy,

Pharmacy, other

© 2026 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, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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