Ordonez Alvaro A, Wintaco Luz M, Mota Filipa, Restrepo Andres F, Ruiz-Bedoya Camilo A, Reyes Carlos F, Uribe Luis G, Abhishek Sudhanshu, D'Alessio Franco R, Holt Daniel P, Dannals Robert F, Rowe Steven P, Castillo Victor R, Pomper Martin G, Granados Ulises, Jain Sanjay K
Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Sci Transl Med. 2021 Apr 14;13(589). doi: 10.1126/scitranslmed.abe9805.
represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[F]fluoro-d-sorbitol (F-FDS) can selectively detect infections in murine models. Here, we demonstrate that uptake of F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed infection or other pathologies demonstrated that F-FDS PET/CT was safe, could rapidly detect and localize infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use F-FDS from commercially available 2-deoxy-2-[F]fluoro-d-glucose (F-FDG) at room temperature. In a hamster model, F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary pneumonia-a leading cause of complications in hospitalized patients with COVID-19. These data support F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.
是人类中最大的细菌病原体群体，可导致严重的深部感染，常引发败血症或死亡。它们也是多重耐药（MDR）感染的主要原因，一些菌种被视为生物威胁病原体。需要能够特异性定位病原体的非侵入性全身分析工具，但目前尚无此类技术。我们之前证明，使用2-脱氧-2-[F]氟-D-山梨醇（F-FDS）的正电子发射断层扫描（PET）可在小鼠模型中选择性检测感染。在此，我们证明细菌对F-FDS的摄取是通过一条代谢保守的山梨醇特异性途径发生的，临床菌株（包括MDR分离株）在体外对F-FDS摄取迅速。对26例前瞻性纳入的微生物学确诊感染或其他病症患者进行的全身F-FDS PET/计算机断层扫描（CT）显示，F-FDS PET/CT是安全的，能够快速检测和定位由药敏或MDR菌株引起的感染，并将它们与无菌性炎症或癌性病变区分开来。对同一患者进行的重复成像监测了抗生素疗效，PET信号的降低与临床改善相关。为便于使用F-FDS，我们开发了一种独立的固相柱，可在室温下从市售的2-脱氧-2-[F]氟-D-葡萄糖（F-FDG）快速（<10分钟）配制即用型F-FDS。在仓鼠模型中，F-FDS PET/CT还区分了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）肺炎与继发性肺炎，继发性肺炎是COVID-19住院患者并发症的主要原因。这些数据支持F-FDS作为一种具有临床应用价值的创新且易于获得的病原体特异性PET技术。
