Evaluation of99mTc-immunoglobulins for imaging infection in the rat

Abstract

SummaryThree immunoglobulin molecules were evaluated as infection imaging agents in a rat model of S. aureas infection:99m 99m Tc-human immunoglobulin (HIG) and 99m Tc-rat immunoglobulin (RIG). Infliximab is a chimeric monoclonal antibody specific for human tumour necrosis factor alpha (TNFa). Tc-HIG was chosen as an exogenous protein and 99m 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 II -methylenediphosphonic acid, cold kit formulations were prepared. Native and reduced infliximab were tested for rat TNFa binding ability in vitro. A focal intramuscular infection of S. aureus (1 Â 10 8 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. 99m 99m Tc-HIG and 99m Tc-RIG were prepared with 595% radiochemical purity from stable cold kits.Results from the organ assay gave infected (target) to non-infected (control) muscle ratios for 99m Tc-infliximab as 5.7 AE 0.8, 7.1 AE 1.2, 99m Tc-HIG gave 3.1 AE 1.1, 7.8 AE 1.2, and 99m Tc-RIG 7.9 AE 0.3, 12.5 AE 1.5 at 1 and 4 h, respectively. Infliximab and Sn II -infliximab did not bind to rat TNFa by the in vitro assay. Although lacking specific affinity for TNFa, 99m Tc-infliximab accumulated at infectious sites in vivo. 99m Tc-infliximab gave similar infection uptake ratios to 99m Tc-HIG at 1 and 4 h, but these proteins were inferior in comparison to 99m Tc-RIG, and is likely to be due to

Effects of 99mTc sestamibi on antioxidant defense system and lipid peroxidation in the heart of Sprague Dawley rats

“…Rats were anesthetized with a cocktail of ketamine hydrochloride (90 mg/kg) and xylazine (10 mg/kg) administered intraperitoneally. Under anesthesia, each rat received a bolus intravenous injection of 99m Tc sestamibi (25 MBq) as a reference agent through the tail vein (Tsopelas et al, 2006). Rats were killed by dissection 60 min after the injection of radiopharmaceutical.…”

“…Under anesthesia, each rat received a bolus intravenous injection of 99mTc sestamibi (25 MBq) as a reference agent through the tail vein (Tsopelas et al, 2006). Rats were killed by dissection 60 min after the injection of radiopharmaceutical.…”

Radiotracers Used for the Scintigraphic Detection of Infection and Inflammation

“…The modified hinge area is sufficiently distant from the V H /V L sites in the immunoglobulin, allowing free interaction with the antigen it was designed for. This was shown for 99m Tc-infliximab, a chimeric mAb [75 : 25, human : mouse] specific for TNF α [ 70 ]. In this study reduced-infliximab retained its specificity for the human antigen, and after its reconstitution as a cold kit formulation, 99m Tc-infliximab was also specific.…”

“…Usually a stannous salt of MDP, tartrate, and so forth facilitates 99m Tc-pertechnetate reduction. The efficacy of 99m Tc-hIgG as the control molecule versus 99m Tc-rat(r)-IgG in a rat model of S. aureus muscle infection was previously examined [ 70 ]. Even though 99m Tc-rIgG was prepared from allogeneic immunoglobulin, the results for this radiotracer showed a T : B ratio of 13 at 4 hours pi, superior to 99m Tc-hIgG ratio of 8 at the same time point, and uptake was clearly visible on the whole body images ( Figure 5 ).…”

Sentinel Lymph Node Imaging and Biopsy in Breast Cancer

“…Tsopelas ve ark. Tc-99m işaretli İPİG, rat immünoglobulin (RİG) ve infliksimab ile ratlarda enfeksiyon çalışmış ve 1. ve 4. saat görüntülerinde enfeksiyon yerinde en yüksek tutulumun Tc-99m RİG ile olduğunu rapor etmiştir (47).…”