RESUMEN
Currently, there are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. Fluorescence and photoacoustic imaging are cost-effective imaging modalities that can be used to noninvasively diagnose bacterial infections when paired with a molecularly targeted infection imaging agent. Here, we develop a fluorescent derivative of maltotriose (Cy7-1-maltotriose), which is shown to be taken up in a variety of gram-positive and gram-negative bacterial strains in vitro. In vivo fluorescence and photoacoustic imaging studies highlight the ability of this probe to detect infection, assess infection burden, and visualize the effectiveness of antibiotic treatment in E. coli-induced myositis and a clinically relevant S. aureus wound infection murine model. In addition, we show that maltotriose is an ideal scaffold for infection imaging agents encompassing better pharmacokinetic properties and in vivo stability than other maltodextrins (e.g. maltohexose).
Asunto(s)
Colorantes Fluorescentes/administración & dosificación , Imagen Molecular/métodos , Miositis/diagnóstico por imagen , Infección de la Herida Quirúrgica/diagnóstico por imagen , Trisacáridos/administración & dosificación , Animales , Carbocianinas/administración & dosificación , Carbocianinas/química , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Escherichia coli/aislamiento & purificación , Escherichia coli/metabolismo , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/metabolismo , Humanos , Inyecciones Intravenosas , Mediciones Luminiscentes/métodos , Ratones , Microscopía Fluorescente/métodos , Sondas Moleculares/administración & dosificación , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Miositis/microbiología , Técnicas Fotoacústicas/métodos , Ratas , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/metabolismo , Infección de la Herida Quirúrgica/microbiología , Trisacáridos/química , Trisacáridos/metabolismoRESUMEN
The cell adhesion molecule integrin alphavbeta3 is an important player in the process of tumor angiogenesis and metastasis. Antibodies, peptides, peptidomimetics, and small molecule antagonists against integrin alphavbeta3 have been shown to induce endothelial apoptosis, to inhibit tumor angiogenesis, and to increase endothelial permeability. The ability to quantitatively image integrin alphavbeta3 expression in vivo in a noninvasive manner may shed new light into the mechanism of angiogenesis and antiangiogenic treatment efficacy based on integrin antagonism. Tumor integrin expression imaging will also aid in lesion detection, patient stratification, new anti-integrin drug development/validation, as well as treatment monitoring and optimization. This review summarizes the recent advances in multimodality imaging of tumor integrin alphavbeta3 expression using magnetic resonance imaging (MRI), ultrasound, near-infrared (NIR) fluorescence, single photon emission computed tomography (SPECT), and positron emission tomography (PET).