| Summary: | In this work, a method for the preparation of the highly lipophilic labeling synthon [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> 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. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was prepared from oxine (8-hydroxyquinoline) and [<sup>89</sup>Zr]Zr(OH)<sub>2</sub>(C<sub>2</sub>O<sub>4</sub>). 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 <sup>89</sup>Zr-complex was incorporated into liposome formulations. PET/CT imaging of <sup>89</sup>Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 10<sup>6</sup> hiPSCs, each. [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [<sup>89</sup>Zr]Zr(oxinate)<sub>4</sub> 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 <sup>89</sup>Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.
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