Zoller Stephen D, Park Howard Y, Olafsen Tove, Zamilpa Charles, Burke Zachary Dc, Blumstein Gideon, Sheppard William L, Hamad Christopher D, Hori Kellyn R, Tseng Jen-Chieh, Czupryna Julie, McMannus Craig, Lee Jason T, Bispo Mafalda, Romero Pastrana Francisco, Raineri Elisa Jm, Miller Jeffery F, Miller Lloyd S, van Dijl Jan Maarten, Francis Kevin P, Bernthal Nicholas M
Department of Orthopedic Surgery, David Geffen School of Medicine at UCLA, Santa Monica, California, USA.
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California, USA.
JCI Insight. 2019 Feb 7;4(3):e124813. doi: 10.1172/jci.insight.124813.
Spine implant infections portend disastrous outcomes, as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. Current imaging modalities can detect anatomical alterations and anomalies but cannot differentiate between infection and aseptic loosening, diagnose specific pathogens, or delineate the extent of an infection. Herein, a fully human monoclonal antibody 1D9, recognizing the immunodominant staphylococcal antigen A on the surface of Staphylococcus aureus, was assessed as a nuclear and fluorescent imaging probe in a preclinical model of S. aureus spinal implant infection, utilizing bioluminescently labeled bacteria to confirm the specificity and sensitivity of this targeting. Postoperative mice were administered 1D9 probe dual labeled with 89-zirconium (89Zr) and a near infrared dye (NIR680) (89Zr-NIR680-1D9), and PET-CT and in vivo fluorescence and bioluminescence imaging were performed. The 89Zr-NIR680-1D9 probe accurately diagnosed both acute and subacute implant infection and permitted fluorescent image-guided surgery for selective debridement of infected tissue. Therefore, a single probe could noninvasively diagnose an infection and facilitate image-guided surgery to improve the clinical management of implant infections.
脊柱植入物感染预示着灾难性的后果，因为诊断具有挑战性，而且手术根除与脊柱机械稳定性相矛盾。目前的成像方式可以检测解剖结构的改变和异常，但无法区分感染和无菌性松动，无法诊断特定病原体，也无法描绘感染的范围。在此，一种识别金黄色葡萄球菌表面免疫显性葡萄球菌抗原A的全人源单克隆抗体1D9，在金黄色葡萄球菌脊柱植入物感染的临床前模型中被评估为一种核成像和荧光成像探针，利用生物发光标记的细菌来确认这种靶向的特异性和敏感性。给术后小鼠注射用89-锆（89Zr）和近红外染料（NIR680）双重标记的1D9探针（89Zr-NIR680-1D9），并进行PET-CT以及体内荧光和生物发光成像。89Zr-NIR680-1D9探针准确诊断了急性和亚急性植入物感染，并允许进行荧光图像引导手术以选择性清除感染组织。因此，单一探针可以无创地诊断感染并促进图像引导手术，以改善植入物感染的临床管理。
