PDF(Pubmed)
Abstract：
Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([68Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [68Ga]Ga-SKN by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis, but no uptake by Candida glabrata, C. albicans, or Aspergillus fumigatus, demonstrated its specificity to bacterial species. Whole-body [68Ga]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 ex vivo 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 [68Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.
摘要：
镓68标记的铁载体作为放射性示踪剂已经引起了人们对原位感染特异性成像诊断的兴趣。这里,我们报告放射性标记，体外筛选，和镓-68标记的裂开肽（[68Ga]Ga-SKN）的体内药代动力学（PK）作为一种新的潜在放射性示踪剂用于成像细菌感染。我们放射性标记SKN的放射化学纯度≥95%。我们的体外研究证明了它的亲水特性，中性pH稳定性,以及在人血清中的短期稳定性和对转移螯合。大肠杆菌对[68Ga]Ga-SKN的体外吸收，铜绿假单胞菌,金黄色葡萄球菌,和表皮葡萄球菌,但没有被光滑念珠菌吸收，C.白色念珠菌,或者烟曲霉,证明了它对细菌物种的特异性。健康小鼠的全身[68Ga]Ga-SKN正电子发射断层扫描（PET）与计算机断层扫描（CT）相结合显示出快速的肾脏排泄，没有或很少有器官摄取。随后的离体生物分布类似于这种快速PK，具有快速的肾脏排泄，血液滞留最少，没有主要器官摄取，并且在注射后60分钟后显示示踪剂在尿液中的一些解离。这些发现保证了对[68Ga]Ga-SKN作为用于感染成像的细菌特异性放射性示踪剂的进一步评估。
