Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has been functionalized with NOTA to allow complexation to ⁶⁸Ga (⁶⁸Ga-NOTA-UBI). We herein assess the cytotoxicity and radiation dosimetry for ⁶⁸Ga-NOTA-UBI and a first-in-human evaluation to diagnose infectious processes. Methods: Cytotoxicity was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes. Tracer susceptibility was studied in vitro using different bacterial and fungal strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry were performed on nonhuman primates. Two healthy volunteers and 3 patients with suspected infection underwent ⁶⁸Ga-NOTA-UBI PET/CT imaging. Results: Negligible cytotoxicity was determined for NOTA-UBI. ⁶⁸Ga-NOTA-UBI showed moderate blood clearance (29-min half-life) and predominant renal clearance in nonhuman primates. Human radiation dose estimates indicated the bladder wall as the dose-critical tissue (185 μSv/MBq), followed by the kidneys (23 μSv/MBq). The total absorbed body dose was low (<7 μSv/MBq); the effective dose was estimated at 17 μSv/MBq. ⁶⁸Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3 patients. Conclusion: ⁶⁸Ga-NOTA-UBI is considered a nontoxic, safe-to-administer radiopharmaceutical unlikely to cause adverse effects in humans. The favorable tracer biodistribution and the first-in-human results will make ⁶⁸Ga-NOTA-UBI PET/CT an encouraging future diagnostic technique with auxiliary clinical relevance.

Ubiquicidin是一种抗菌肽，具有很大的潜力，可用于传染病的核成像，因为其富含阳离子的片段TGRAKRRMQYNRR（UBI）已通过NOTA进行了功能化，从而可以复合至⁶⁸ Ga（⁶⁸ Ga-NOTA-UBI）。我们在本文中评估了⁶⁸ Ga-NOTA-UBI的细胞毒性和放射剂量，并首次在人体内进行评估以诊断感染过程。方法：评价了绿猴肾上皮（Vero）细胞和MT-4白细胞的细胞毒性。在体外使用不同的细菌和真菌菌株研究了示踪剂的敏感性。对非人类灵长类动物进行了基于PET / CT的生物分布，药代动力学和辐射剂量测定。两名健康志愿者和三名疑似感染患者接受了⁶⁸ Ga-NOTA-UBI PET / CT成像。结果：对于NOTA-UBI，细胞毒性可忽略不计。⁶⁸Ga-NOTA-UBI在非人类灵长类动物中显示出中等的血液清除率（半衰期为29分钟）和主要的肾脏清除率。人体辐射剂量估算表明，膀胱壁是剂量关键组织（185μSv/ MBq），其次是肾脏（23μSv/ MBq）。总吸收剂量低（<7μSv/ MBq）；有效剂量估计为17μSv/ MBq。⁶⁸ Ga-NOTA-UBI可以诊断3例患者中的3例骨和软组织感染。结论： ⁶⁸ Ga-NOTA-UBI被认为是一种无毒，易于管理的放射性药物，不可能对人类造成不良影响。良好的示踪剂生物分布和人类首创的结果将使⁶⁸ Ga-NOTA-UBI PET / CT成为具有辅助临床意义的令人鼓舞的未来诊断技术。