Evaluation of Tc-99m-immunoglobulins for imaging infection in the rat
Date
2006
Authors
Tsopelas, C.
Penglis, P.
Miller, D.
Rischmueller, M.
Bartholomeusz, F.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Labelled Compounds and Radiopharmaceuticals, 2006; 49(10):915-928
Statement of Responsibility
Chris Tsopelas, Stan Penglis, Darren Miller, Maureen Rischmueller, F. Dylan L. Bartholomeusz
Conference Name
Abstract
<jats:title>Abstract</jats:title><jats:p>Three immunoglobulin molecules were evaluated as infection imaging agents in a rat model of <jats:italic>S. aureas</jats:italic> infection: <jats:sup>99m</jats:sup>Tc‐infliximab, <jats:sup>99m</jats:sup>Tc‐human immunoglobulin (HIG) and <jats:sup>99m</jats:sup>Tc‐rat immunoglobulin (RIG). Infliximab is a chimeric monoclonal antibody specific for human tumour necrosis factor alpha (TNFα). <jats:sup>99m</jats:sup>Tc‐HIG was chosen as an exogenous protein and <jats:sup>99m</jats:sup>Tc‐RIG as an endogenous marker. Each immunoglobulin was treated with 2‐mercaptoethanol and the reduced antibody was isolated by size exclusion chromatography. In combination with Sn<jats:sup>II</jats:sup>‐methylenediphosphonic acid, cold kit formulations were prepared. Native and reduced infliximab were tested for rat TNFα binding ability <jats:italic>in vitro</jats:italic>. A focal intramuscular infection of <jats:italic>S. aureus</jats:italic> (1 × 10<jats:sup>8</jats:sup> colony forming units) was induced in the left thigh muscle of rats, that developed for 24 h. In separate experiments each tracer was administered by intravenous injection, then whole body scintigraphic imaging and biodistribution studies were performed at 1 and 4 h later. <jats:sup>99m</jats:sup>Tc‐infliximab, <jats:sup>99m</jats:sup>Tc‐HIG and <jats:sup>99m</jats:sup>Tc‐RIG were prepared with ⩾95% radiochemical purity from stable cold kits. Results from the organ assay gave infected (target) to non‐infected (control) muscle ratios for <jats:sup>99m</jats:sup>Tc‐infliximab as 5.7±0.8, 7.1±1.2, <jats:sup>99m</jats:sup>Tc‐HIG gave 3.1±1.1, 7.8±1.2, and <jats:sup>99m</jats:sup>Tc‐RIG 7.9±0.3, 12.5±1.5 at 1 and 4 h, respectively. Infliximab and Sn<jats:sup>II</jats:sup>‐infliximab did not bind to rat TNFα by the <jats:italic>in vitro</jats:italic> assay. Although lacking specific affinity for TNFα, <jats:sup>99m</jats:sup>Tc‐infliximab accumulated at infectious sites <jats:italic>in vivo</jats:italic>. <jats:sup>99m</jats:sup>Tc‐infliximab gave similar infection uptake ratios to <jats:sup>99m</jats:sup>Tc‐HIG at 1 and 4 h, but these proteins were inferior in comparison to <jats:sup>99m</jats:sup>Tc‐RIG, and is likely to be due to increased clearance associated with the foreign protein structure. Copyright © 2006 John Wiley & Sons, Ltd.</jats:p>