Poster Presentation Royal Australian Chemical Institute National Congress 2026

Synthesis and evaluation of mitochondria-targeted triphenylphosphonium–NODA ligands for Al/18F and 68Ga radiolabelling (#524)

Neha Agarwal 1 , Louis Rendina 1
  1. University of Sydney, Sydney, NSW, Australia

Theranostic and personalized medicine have emerged as promising strategies for improving oncologic patient care and enabling earlier therapeutic intervention. Among available radiochemical approaches, Al/18F and 68Ga based chemistry is particularly attractive for theranostic applications because of their favourable imaging characteristics, with aluminium fluoride and gallium mediated radiolabelling offering an efficient route for preparation of new diagnostic agents for positron emission tomography (PET)1,2. In parallel, triphenylphosphonium-based cations, which possess lipophilicity and a delocalized positive charge, are well established as mitochondrial-targeting motifs and serve as effective carriers for drug delivery3. In this study, we report the synthesis and evaluation of a series of new ligands with the potential to chelate Al/18F and ⁶⁸Ga. of mitochondria-targeted triphenylphosphinonium–NODA derivatives, with direct relevance to PET imaging for solid tumours and heart perfusion. Triphenylphosphonium-functionalized NODA ligands were prepared by means of modular synthetic route and were fully characterized NMR spectroscopy, HPLC, and mass spectrometry. Efficient ⁶⁸Ga and Al/18F incorporation was achieved under mild conditions with compatible chemistry, affording metal complexes with favourable stability in aqueous media. Importantly, the introduction of the triphenylphosphosphonium moiety did not adversely affect metal coordination, demonstrating the compatibility of mitochondrial-targeting groups with Al/18F and ⁶⁸Ga chemistry. Collectively, our work establishes triphenylphosphonium–NODA scaffolds as a versatile coordination platform for Al/18F and 68Ga radiolabelling and provides design insights for the development of mitochondria-targeted based PET radiotracers.

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  2. McBride, W. J., Sharkey, R. M., & Goldenberg, D. M. (2013). Radiofluorination using aluminum-fluoride (Al18F). EJNMMI research, 3(1), 36.
  3. Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., ... & Kalyanaraman, B. (2017). Mitochondria-targeted triphenylphosphonium-based compounds: syntheses, mechanisms of action, and therapeutic and diagnostic applications. Chemical reviews, 117(15), 10043-10120.