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

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.