Predicting tumour and organ dose in α-radiopharmaceutical therapy: a ⁸⁹Zr-based dosimetric approach for ²²⁵Ac.

Authors

Robin I J Merkx, Simone C Kleinendorst, Mark Rijpkema, Gerben M Franssen, Alfred Morgenstern, Frank Bruchertseifer, Michael P Wheatcroft, Egbert Oosterwijk, Peter F A Mulders, Mark Konijnenberg, Sandra Heskamp

Published in

European journal of nuclear medicine and molecular imaging. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

The aim of this study was to assess whether zirconium-89 (⁸⁹Zr)-labelled antibodies can act as a surrogate for actinium-225 (²²⁵Ac)-labelled antibodies to predict tumour- and organ dose. To this end, we performed ex vivo biodistribution and dosimetry studies with two anti-CAIX antibodies (hG250 and FcRn(-)hG250), radiolabelled with ⁸⁹Zr and ²²⁵Ac, in a renal cell carcinoma mouse model.
BALB/c nude mice bearing subcutaneous SK-RC-52 tumours were injected intravenously with 25-50 kBq ²²⁵Ac-labelled or 1 MBq ⁸⁹Zr-labelled anti-CAIX antibody, at equal protein dose. Organ and tumour absorbed doses were calculated based on the uptake data at 4, 24, 72, and 168 h for FcRn(-)hG250 and 24, 72, and 168 h for hG250. The predictive value of ⁸⁹Zr for ²²⁵Ac was evaluated in both groups, by comparing the predicted ²²⁵Ac absorbed dose (based on ⁸⁹Zr-antibody) and the measured ²²⁵Ac absorbed dose.
The biodistribution profile of the theranostic pair ⁸⁹Zr/²²⁵Ac was comparable for FcRn(-)hG250. For hG250, significant discrepancies between tumour, spleen and liver uptake were observed. The predicted ²²⁵Ac tumour dose was overestimated by 3.9 ± 2.0 Gy (6 ± 50.6%) and underestimated by 1413.7 ± 629.1 Gy (69 ± 44.5%) in the FcRn(-)hG250 and hG250 groups, respectively. The deviation of the predicted versus measured ²²⁵Ac-dose in off-target organs was most notable in liver and spleen for both antibodies.
This study highlights variability in the predictive accuracy of the ⁸⁹Zr/²²⁵Ac theranostic pair for tumour and organ dosimetry in a ccRCC mouse model, depending on the antibody used. FcRn(-)hG250 enabled accurate tumour dose estimation, whereas hG250 showed mismatched uptake limiting prediction, possibly due to inherent differences in the properties and biological effects of both ²²⁵Ac and ⁸⁹Zr. These findings underscore the need to further investigate how ⁸⁹Zr-PET can be used for ²²⁵Ac-TRT dose prediction.

PMID:
42455315
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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