Institute of Pharmaceutical Science, Faculty of Life Science and Medicine, King's College London, London SE1 9NH, United Kingdom.
School of Biomedical Engineering and Imaging Sciences, Faculty of Life Science and Medicine, King's College London, London SE1 7EH, United Kingdom.
ACS Infect Dis. 2024 Aug 9;10(8):2615-2622. doi: 10.1021/acsinfecdis.4c00067. Epub 2024 Jul 16.
Gallium-68-labeled siderophores as radiotracers have gained interest for the development of infection-specific imaging diagnostics. Here, we report radiolabeling, screening, and pharmacokinetics (PK) of gallium-68-labeled schizokinen ([Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. uptake of [Ga]Ga-SKN by , , , and , but no uptake by , , or , demonstrated its specificity to bacterial species. Whole-body [Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.
镓-68 标记的铁载体作为放射性示踪剂,因其可用于开发针对感染的特异性成像诊断而受到关注。在此,我们报告了新型潜在放射性示踪剂镓-68 标记的裂裥菌素 ([Ga]Ga-SKN) 的放射性标记、筛选和药代动力学 (PK)。我们以≥95%的放射化学纯度标记了 SKN。我们的研究表明其具有亲水性、中性 pH 稳定性以及在人血清中和向转铁蛋白转移方面的短期稳定性。[Ga]Ga-SKN 的摄取仅见于 、 、 、 和 ,而 、 或 则无摄取,表明其对细菌物种具有特异性。健康小鼠的全身 [Ga]Ga-SKN 正电子发射断层扫描 (PET) 与计算机断层扫描 (CT) 结合显示,其具有快速的肾脏排泄,无或仅有最小的器官摄取。随后的生物分布与这种快速 PK 相似,具有快速的肾脏排泄,血液滞留最小,没有主要器官摄取,并在注射后 60 分钟时在尿液中显示出一些示踪剂的解离。这些发现证明了 [Ga]Ga-SKN 作为一种用于感染成像的细菌特异性放射性示踪剂的进一步评估是合理的。