Preparation and biodistribution of ^99mTechenetium labeled ceftiofur: Potential infection-imaging agent.

Cephalosporines are broad spectrum antibiotics, active against both gram+ve and gram-ve bacteria. Ceftiofur, a third generation Cephalosporin was labeled with ^99mTechenetium to evaluate its potential in imaging infections.

To establish a labeling protocol and evaluate biokinetics of the ^99mTc-Ceftiofur.

Labeling of Ceftiofur with ^99mTc was carried out by using stannous chloride as the reducing agent. A typical labeling procedure would be: 5.0 ± 0.5 mg Ceftiofur dissolved in 80l of 2M NaOH solution, 300g SnCl₂ and ^99mTcO^4-(∼10mCi in 0.2ml saline) in a final reaction volume of 1ml made up with distilled water. The pH of the final solution was adjusted to 6–7 using 1M NaH₂PO solution. Radiochemical purity of ^99mTc-Ceftiofur was determined by thin layer chromatography using saline and methanol: water (70:30) as mobile phases. The ^99mTc-Ceftiofur was injected into normal, healthy Balb/c mice through the tail vein for biodistribution studies. Animals were sacrificed at 30min, 1h, 3h, and 24h post-injection and radioactivity in various organs was counted to measure the percent uptake of the injected dose.

The radiochemical purity (RCP) of ^99mTc-Cefteofur was >90%. The in vitro stability of the complex was confirmed by carrying out RCP check over period of 4 hours. The circulating levels were a maximum (5%) at 30 min and, thereafter, decreased to 0.9% at 24h. The liver uptake was also maximum (8.7%) at 30min and decreased to 2.1% at 24h. The muscle uptake peaked (1.4%) at 3h. Bone and brain uptake was found to be maximum 1.7% and 2% at 3h respectively. Excretion of the compound was both through the renal system and GI-route. Renal clearance was a maximum (7.4%) at 3h. The small-intestines had >11% up to 1h and decreased to 0.9% at 24h. The activity in the large-intestine was a ∼ 2% up to 1h and a maximum of 14% at 3h, decreasing to 3.5% at 24h.

Thus, in normal animals, the clearance appears to be through the hepatic and renal routes, and the drug remains in circulation for a reasonably long period of over 3hours. This means that infection foci will get adequate exposure to the ^99mTc-Ceftiofur and bind it.

The labeling protocol of ^99mTc-Cefteofur was established and the radiochemical purity of the complex was >90%. The normal distribution shows hepatic and renal excretion of the drug. The prolonged presence of drug in circulation will be an added advantage for infection imaging, which needs to be evaluated in animal models.