Abstract

GOUWS, Christiaan A. et al. Gallium-68-NODASA-Functionalized D-Lysine Radiosynthesis and first-line in vitro characterization - a potential PET imaging agent for infection. S.Afr.j.chem. (Online) [online]. 2025, vol.79, pp.81-95. ISSN 1996-840X.  https://doi.org/10.17159/0379-4350/2025/v79a09.

The advancement of new Positron Emission Tomography (PET) radiotracers for differentiating bacterial infections from sterile inflammation is essential for accurate diagnosis and treatment monitoring. D-amino acid-based probes have shown promise for bacterial imaging due to their selective peptidoglycan incorporation. However, host enzyme-mediated racemization of radiolabeled D-amino acids and limited tissue penetration of fluorescence signal of fluorescent D-amino acids limits their in vivo performance. Herein, we report the successful chemical synthesis, optimized radiosynthesis, and the required first-line in vitro characterization of [⁶⁸Ga]Ga-NDL-1 (NDL = NODASA D-lysine; NODASA = 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) (the L-isomeric compound, aka. [⁶⁸Ga]Ga-NLL-1 was evaluated in parallel as the control). Robust radiolabeling was achieved within 60 minutes using the optimized radiolabeling method, featuring the consistent production of very good radiochemical yields (81.7 ± 3.2%), apparent molar activities (17.1 ± 0.8 GBq/µmol) and with excellent radiochemical purities (97.7 ± 0.5%), free of ⁶⁸Ga-colloids; therefore, deemed suitable for future intravenous administration and micro-PET imaging applications. [⁶⁸Ga]Ga-NDL-1 was highly stable during prolonged incubation in the presence of 1000-times excess of EDTA (>93%) as well as a during a 2-hour exposure to plasma (>97%). [⁶⁸Ga]Ga-NLL-1 and [⁶⁸Ga]Ga-NDL-1 showed minimal overall blood cell binding (<12%) or plasma protein binding (<15%). Results justify further investigation of [⁶⁸Ga]Ga-NDL-1 as a potential PET imaging agent of infection.

Keywords : D-amino acid; peptidoglycan; positron emission tomography; bacterial-specific; radiolabeling; radiochemical characterization; imaging of infection.

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