Development of novel ligands for emerging radiometal isotopes

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John Wiley & Sons, Inc.
Background: The use of radiometals (non-Tc, non-Re) in targeted diagnosis and radiotherapy of different disease states has increased significantly over the last 15 years. ANSTO LifeSciences radiometals program seeks to provide a suite of radiometal tools for use in PET imaging and therapeutic modalities to improve upon the existing technologies which are currently dominated by 99mTc. This will enable researchers and clinicians to study and diagnose diseases with a greater efficacy and efficiency. Method: Many of the ligands currently available for radiometals have numerous drawbacks , including unfavourable in vivo properties such as thermodynamic and kinetic stability and poor lipophilicity. We are developing new ligand systems to have improved radiometal specificity while including design flexibility allowing us to manipulate properties such as biodistribution patterns, excretion rates, pharmacokinetics, thermodynamics and in vivo stability. The synthesis should be straightforward and cost effective and have the potential for bioconjugation in the initial design. Complexation studies are performed in vitro to assess the ligands suitability. Results: We are developing ligand systems for 68Ga, 89Zr, 64Cu, 90Y and 177Lu. We have prepared a novel analogue of the ubiquitous ligand NOTA (Figure 1, b); our system replaces the biologically labile carboxylic acid with a corresponding, biologically inert isotere, a tetrazole. This manipulation should provide additional stability and increased complex lipophilicity. Our studies have shown that a tetrazole analogue of NOTA (Figure 1, b) forms stable cold-metal complexes with potential PET metals of interest such as Ga3+. Conclusion: ANSTO LifeSciences provides a complete synthetic ligand and metal complex program, complementing its broader Radiometals Program. The aim of which is to provide an array of clinically relevant ligands that can be used in multiple applications for specific metal radiopharmaceuticals for improved patient outcomes. © 2013 John Wiley & Sons
Open Access
Radiotherapy, ANSTO, Positron computed tomography, Diseases, In vitro, Ligands, Thermodynamics, Kinetics
Ashford, M., Burgess, L., Cheah, W. C., Krause-Heuer, A., Fraser, B., Greguric, I., & Lengleek, N. (2015). Development of novel ligands for emerging radiometal isotopes. Poster presented at the 43rd Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine (ANZSNM), 11-15 April, 2013, Perth Convention and Exhibition Centre, Perth, Australia. In Internal Medicine Journal, 43 (S1), 34. doi:10.1111/imj.12133