Improving Routine 89Zr‐Immuno‐PET Applications: Mild Iron Removal Can Favor the Use of Fe‐DFO‐N‐suc‐TFP Ester Over p‐NCS‐Bz‐DFO

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 67; no. 8; pp. 280 - 287
• Main Authors: Wuensche, Thomas E., Nauta, Sabine, Dongen, Guus A. M. S., Vugts, Danielle J.
• Format: Journal Article
• Language: English
• Published: Bognor Regis Wiley Subscription Services, Inc 30-06-2024
• Subjects: Conjugation; deferiprone; Deferoxamine; DFO; Edetic acid; Ethylenediamine; Ethylenediaminetetraacetic acids; immuno‐PET; Iron; Iron 59; pH effects; Radiochemistry; Radiolabelling; radiometals; Zirconium isotopes; zirconium‐89
• ISSN: 0362-4803; 1099-1344; 1099-1344
• DOI: 10.1002/jlcr.4097

ABSTRACT
A key aspect for the applicability of 89Zr‐radioimmunoconjugates is inert modification and radiolabeling. The two commercially available bifunctional variants of the siderophore desferrioxamine (DFO), Fe‐DFO‐N‐suc‐TFP‐ester and p‐NCS‐Bz‐DFO, are most often used for clinical 89Zr‐immuno‐PET. The use of Fe‐DFO‐N‐suc‐TFP‐ester is advantageous with regard to higher radiolysis stability and more facile assessment of radiochemical purity as well as chelator‐to‐mAb ratio. However, not all mAbs withstand the Fe‐removal step at relatively low pH (4–4.5) using EDTA, which is needed after conjugation to allow 89Zr labeling. In this study, it was investigated whether hydroxybenzyl ethylenediamine (HBED) or the clinically approved deferiprone (DFP) can serve as an alternative for EDTA to establish a pH‐independent mild method for Fe‐removal and thereby broaden the applicability of Fe‐DFO‐N‐suc‐TFP‐ester. Carrier‐added [59Fe]Fe‐DFO‐N‐suc‐TFP‐ester was used for mAb modification to enable direct tracking of the Fe‐removal efficiency under various conditions. Whereas incomplete Fe‐removal with HBED was observed at pH 5 or higher, Fe‐removal with DFP was possible at a broad pH range (4–9). This provides a mild, pH‐independent method for Fe‐removal, improving the applicability and attractiveness of Fe‐DFO‐N‐suc‐TFP‐ester for 89Zr‐mAb preparation.
A pH‐independent Fe‐removal method for Fe‐DFO‐N‐suc‐mAbs using deferiprone (DFP) instead of EDTA is presented. The use of Fe‐DFO‐N‐suc‐TFP‐ester as a chelator is no longer restricted to mAbs that can withstand the Fe‐removal at pH 4‐4.5 with EDTA, broadening its for clinical use and making it a favorable alternative to p‐Bz‐NCS‐DFO.