title: Radiolabeled oligosaccharides nanoprobes for infection imaging.
abstract: Breast milk oligosaccharides act as soluble receptors for different pathogens which protect the newborn child from infection. The differentiation between loosening of prosthesis due to infective pathology septic or otherwise aseptic plays an important role in the patient management. We have labeled hydroxypropyl-β-cyclodextrin, oligosaccharide derivative, with technetium-99m ((99m)Tc-HPβCD). The quality control of (99m)Tc-HPβCD was done by ITLC and characterized by electron microscopy and (1)H-nuclear magnetic resonance. The route of excretion of (99m)Tc-HPβCD nanoparticulate radiopharmaceutical was assessed in rats. Nanoparticles (99m)Tc HPβCD were injected in human subjects with clinically confirmed infected knee joints. Docking studies were done for ligand - protein interaction. The (99m)Tc-HPβCD was stable with good radiochemical yield (>98%) at pH 4.0 and 6.5. For single patient dose, 0.5-1.0mg HPβCD quantity was sufficient. (99m)Tc HPβCD was observed to form nanoparticles of 60-180 μm. The (1)H NMR studies revealed the binding of (99m)Tc at C-8/H-8 position of HPβCD. The excretion of (99m)Tc HPβCD showed renal route of excretion. Docking studies demonstrated the interaction between HPβCD and bacterial maltose binding protein (MBP). The differentiation between septic and aseptic loosening was also evident on single photon emission tomography (SPET). In conclusion, these data indicated that (99m)Tc HPβCD is a promising radiopharmaceutical and may serve as molecular nanoprobe for infection imaging.
authors.affiliation: Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Jaya
authors.initials: J
authors.lastname: Shukla
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Arora
authors.forename: Prakash P
authors.initials: PP
authors.lastname: Kotwal
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Arun
authors.initials: A
authors.lastname: Malhotra
authors.forename: Guru Pad
authors.initials: GP
authors.lastname: Bandopadhyaya
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001424:Bacterial Infections / Q000175:diagnosis*; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D007553:Isotope Labeling; D058619:Maltose-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D015609:Organotechnetium Compounds; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D058619:Maltose-Binding Proteins; D015609:Organotechnetium Compounds; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin