[68Ga]Ga-THP-Tetrazine for bioorthogonal click radiolabelling: Pretargeted PET imaging of liposomal nanomedicines

• DOI: 10.26434/chemrxiv-2024-7w2hn
• Publication Date: 2024-01-31T13:10:45Z
• Authors: Aishwarya Mishra; Amaia Carrascal-M...; Jana Kim; Rafael T. M. de R...
• Keywords: Bioorthogonal Chemistry; Tetrazine; PET Imaging

Pretargeted PET imaging using bioorthogonal chemistry is a leading strategy for the tracking of long-circulating agents such as antibodies and nanoparticle-drug delivery systems with short-lived isotopes. Here, we report synthesis, characterisation in vitro/vivo evaluation new 68Ga-based radiotracer [68Ga]Ga-THP-Tetrazine ([68Ga]Ga-THP-Tz) click radiochemistry vivo labelling slow pharmacokinetics. THP-tetrazine (THP-Tz) can be radiolabelled to give [68/67Ga]Ga-THP-Tz at room temperature less than 15 minutes excellent radiochemical stability vitro vivo. [68Ga]Ga-THP-Tz was tested pretargeted stealth PEGylated liposomes, chosen clinically-approved platform nanoparticle-based drug delivery, their known properties. To achieve this, liposomes were functionalised synthesised transcyclooctene (TCO) modified phospholipid. Radiolabelling TCO-PEG-liposomes demonstrated human serum, both healthy mice syngeneic cancer murine model (WEHI-164 fibrosarcoma). Interestingly data revealed that able radiolabel present liver spleen, not those blood pool or tumour. Overall, these results demonstrate potential imaging/therapy but also some unexpected limitations this system.