Maltohexaose-indocyanine green (MH-ICG) for near infrared imaging of endocarditis

• Published in: PloS one Vol. 16; no. 3; p. e0247673
• Main Authors: Takemiya, Kiyoko, Røise, Joachim J, He, Maomao, Taing, Chung, Rodriguez, Alexander G, Murthy, Niren, Goodman, Mark M, Taylor, W Robert
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2021; Public Library of Science (PLoS)
• Subjects: Animals; Antibiotics; Bacteria; Bacterial diseases; Bacterial infections; Biocompatibility; Bioengineering; Biology and Life Sciences; Biomedical engineering; Cardiac Imaging Techniques - methods; Cardiology; Cell Survival - drug effects; CHO Cells; Coloring Agents - chemistry; Coloring Agents - pharmacokinetics; Cricetulus; Cytotoxicity; Diagnosis; Disease Models, Animal; Disseminated infection; Division; Echocardiography; Editing; Electronic mail; Emitters; Endocarditis; Endocarditis, Bacterial - diagnostic imaging; Endocarditis, Bacterial - microbiology; Endocarditis, Bacterial - pathology; Engineering and Technology; Fluorescence; Fluorescent dyes; Fluorescent indicators; Fluorine; Fluoroscopic imaging; Funding; Genetic aspects; Glycoconjugates - chemistry; Glycoconjugates - pharmacokinetics; Gram-positive bacteria; Health aspects; Health care facilities; Heart; Heart valves; Heart Ventricles - diagnostic imaging; Heart Ventricles - microbiology; Heart Ventricles - pathology; Humans; Indocyanine Green - chemistry; Indocyanine Green - pharmacokinetics; Infrared imaging; Infrared Rays; Laboratory animals; Male; Maltodextrin; Measurement; Medical imaging; Medicine; Medicine and Health Sciences; Methodology; Oligosaccharides - chemistry; Oligosaccharides - pharmacokinetics; Radioisotopes; Radiology; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Reviews; Staphylococcal Infections - diagnostic imaging; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - growth & development; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Toxicity; United States; Atlanta Georgia; Georgia; California; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0247673

Infectious endocarditis is a life-threatening disease, and diagnostics are urgently needed to accurately diagnose this disease especially in the case of prosthetic valve endocarditis. We show here that maltohexaose conjugated to indocyanine green (MH-ICG) can detect Staphylococcus aureus (S. aureus) infection in a rat model of infective endocarditis. The affinity of MH-ICG to S. aureus was determined and had a Km and Vmax of 5.4 μM and 3.0 X 10-6 μmol/minutes/108 CFU, respectively. MH-ICG had no detectable toxicity to mammalian cells at concentrations as high as 100 μM. The in vivo efficiency of MH-ICG in rats was evaluated using a right heart endocarditis model, and the accumulation of MH-ICG in the bacterial vegetations was 2.5 ± 0.2 times higher than that in the control left ventricular wall. The biological half-life of MH-ICG in healthy rats was 14.0 ± 1.3 minutes, and approximately 50% of injected MH-ICG was excreted into the feces after 24 hours. These data demonstrate that MH-ICG was internalized by bacteria with high specificity and that MH-ICG specifically accumulated in bacterial vegetations in a rat model of endocarditis. These results demonstrate the potential efficacy of this agent in the detection of infective endocarditis.