Site-Selectively Functionalized Albumin with DFO*Maleimide for <sup>89</sup>Zr-Radiolabeling Yields a Metabolically Stable PET Probe that Enables Late Time-Point Tumor Imaging in Mice

Author(s): Julia Kronberger, Theresa Balber, Hemma Schueffl, Raphaela Wahrmann, Anja Federa, Mathias Gradl, Marie R. Brandt, Thomas Wanek, Markus Mitterhauser, Christian R. Kowol, Thomas L. Mindt, Petra Heffeter
Abstract: Human serum albumin (HSA) is a clinically validated drug carrier that improves drug delivery to tumor tissues. However, clinical imaging strategies are lacking to stratify patients who will benefit from HSA-bound drugs. In this study, we site-selectively radiolabeled HSA with zirconium-89 (⁸⁹Zr), using the octadentate chelator DFO*, to provide an imaging probe with enhanced stability and sufficient half-life to elucidate the long-term (tumoral) albumin homeostasis. [⁸⁹Zr]Zr-DFO*malHSA demonstrated excellent metabolic stability and high tumor uptake in a longitudinal PET study (72 h p.i.) using a subcutaneous colorectal cancer allograft model (CT26). Preliminary results also showed enhanced enrichment of the PET probe in an intraperitoneally injected CT26 model indicating the role of the EPR effect not only in subcutaneous models. Consequently, [⁸⁹Zr]Zr-DFO*malHSA is a promising tool to image albumin accumulation in malignant tissues and should be further (pre)clinically developed as a companion diagnostic agent for patient stratification in trials with albumin-binding drugs.
Organisation(s): Department of Inorganic Chemistry, Joint Applied Medicinal Radiochemistry Facility
External organisation(s): Vienna Doctoral School in Chemistry (DoSChem), Medizinische Universität Wien
Journal: Journal of Medicinal Chemistry
Volume: 68
Pages: 12925-12939
No. of pages: 15
ISSN: 0022-2623
DOI: https://doi.org/10.1021/acs.jmedchem.5c00803
Publication date: 06-2025
Peer reviewed: Yes
Austrian Fields of Science 2012: 403020 Veterinary medical chemistry, 301904 Cancer research
ASJC Scopus subject areas: Molecular Medicine, Drug Discovery
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Portal url: https://ucrisportal.univie.ac.at/en/publications/8cb4cf8f-ec01-4977-b3c4-176cf0295a96