Simplified ⁸⁹Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells

• Main Authors: Andras Polyak (Author), Jens P. Bankstahl (Author), Karen F. W. Besecke (Author), Constantin Hozsa (Author), Wiebke Triebert (Author), Rajeswara Rao Pannem (Author), Felix Manstein (Author), Thomas Borcholte (Author), Marcus Furch (Author), Robert Zweigerdt (Author), Robert K. Gieseler (Author), Frank M. Bengel (Author), Tobias L. Ross (Author)
• Format: Book
• Published: MDPI AG, 2021-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics13071097; 1999-4923
• Keywords: nanoparticles; liposomes; cell labeling; imaging; PET; nanomedicine; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 13, Iss 7, p 1097 (2021)

In this work, a method for the preparation of the highly lipophilic labeling synthon [⁸⁹Zr]Zr(oxinate)₄ was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [⁸⁹Zr]Zr(oxinate)₄ was prepared from oxine (8-hydroxyquinoline) and [⁸⁹Zr]Zr(OH)₂(C₂O₄). Earlier introduced liquid-liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the ⁸⁹Zr-complex was incorporated into liposome formulations. PET/CT imaging of ⁸⁹Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 10⁶ hiPSCs, each. [⁸⁹Zr]Zr(oxinate)₄ was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [⁸⁹Zr]Zr(oxinate)₄ into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers' in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible ⁸⁹Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.