Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Radiation Applications Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
Chem Biol Drug Des. 2021 Apr;97(4):904-913. doi: 10.1111/cbdd.13817. Epub 2020 Dec 23.
Bacterial infections are a serious risk to human health, and therefore techniques for early detection of infectious foci need to be further developed to begin treatment quickly and achieve better results. Antimicrobial peptides labeled with gamma-emission radio nuclides are important diagnostic radiotracers in nuclear medicine. This study was conducted to evaluate the potential of a Tc-labeled MicrocinJ25 (MccJ25) antimicrobial peptide analog for early detection of infection. For this purpose, a HYNIC conjugated cyclic peptide derivative based on the primary structure of MccJ25 peptide was prepared and labeled by Tc with tricine and EDDA as coligands. The [ Tc-HYNIC/EDDA]-MccJ25 peptide analog showed high radiochemical purity (˃90% (n = 5)) which was stable up to 24 hr after labeling. The radiotracer showed specific uptake to the Escherichia coli (E. coli) bacterial (40.45 ± 5.21%) at 1 hr incubation. High kidneys uptake of radioactivity (4.71 ± 0.84% and 3.76 ± 0.45% ID/g at 1 and 4 hr after injection respectively) demonstrates that most of the whole body clearance was proceeded via the urinary system. Significant radioactivity uptake (1.71 ± 0.34%ID/g) was observed in thigh muscle of mouse with E. coli induced infection at 1 hr after injection. In the blocking test, due to the significant decrease of radioactivity uptake in the infection site (0.62 ± 0.21%ID/g after 1 hr), the specificity of infection uptake was reviled. Despite the high activity of the bladder due to urinary excretion, the infected area was somewhat visible. Hence, the results indicate the potential of this new radiotracer to be used as a diagnostic agent in E. coli infections.
细菌感染对人类健康构成严重威胁，因此需要进一步开发用于早期检测感染病灶的技术，以便快速开始治疗并取得更好的效果。标记有 γ 射线放射性核素的抗菌肽是核医学中重要的诊断放射性示踪剂。本研究旨在评估 Tc 标记的 MicrocinJ25（MccJ25）抗菌肽类似物用于早期检测感染的潜力。为此，制备了一种基于 MccJ25 肽一级结构的 HYNIC 缀合环肽衍生物，并使用 tricine 和 EDDA 作为共配体用 Tc 进行标记。[Tc-HYNIC/EDDA]-MccJ25 肽类似物的放射化学纯度高（>90%（n=5）），标记后 24 小时内稳定。放射性示踪剂在 1 小时孵育时对大肠杆菌（E. coli）细菌的摄取具有特异性（40.45±5.21%）。高肾脏放射性摄取（分别在注射后 1 和 4 小时为 4.71±0.84%和 3.76±0.45%ID/g）表明，大部分全身清除是通过泌尿系统进行的。在注射后 1 小时，在感染的大腿肌肉中观察到显著的放射性摄取（1.71±0.34%ID/g）。在阻断试验中，由于感染部位的放射性摄取显著减少（1 小时后为 0.62±0.21%ID/g），因此揭示了感染摄取的特异性。尽管由于尿液排泄导致膀胱活性很高，但受感染的区域仍可见。因此，这些结果表明这种新的放射性示踪剂有可能用于大肠杆菌感染的诊断剂。
