Preliminary evaluation of technetium-99m-labeled ceftriaxone: infection imaging agent for the clinical diagnosis of orthopedic infection

Objective: In this study we sought to assess the efficacy of a technetium-99m (Tc-99m)-labeled third-generation cephalosporin as an infection imaging agent in the accurate detection of the sites of bacterial infection in vivo.

Design: Ceftriaxone (CRO) was formulated into a ready-to-use single-vial cold kit with a shelf-life of over 6 months and was successfully labeled with technetium. The radiolabeled drug, Tc-99m-CRO, was subjected to the following preclinical evaluations: radiochemical purity, in vitro and in vivo stability, bacterial binding assay, and pharmacokinetic studies in animals and in human patients.

Results: The kit formulation exhibited excellent radiolabeling efficiency (∼99%) and high in vitro and in vivo stability. The radiolabeled drug exhibited slow blood clearance (12% at 4 h), and the high protein binding and excretion pattern of the labeled formulation mimics the reported pharmacokinetic profile of the drug alone. In the animal model, scintigraphy scans showed higher uptake of the radiopharmaceutical in infectious lesions, even at 1 h post-administration, in comparison to inflammatory lesions. The clinical evaluation of Tc-99m-labeled CRO showed a diagnostic accuracy of 83.3%, and a sensitivity and specificity of 85.2% and 77.8%, respectively.

Conclusions: This kit formulation has the potential for imaging bacterial infections with much higher sensitivity and specificity as compared to other Tc-99m-labeled antibiotics available as convenient ready-to-use kits in routine clinical practice.