Development of 99mTc-cefadroxil loaded chitosan nanoparticles as a novel radiotracer for detection of septic and aseptic foci

Early detection of inflammation is critical for preventing disease progression, and nuclear medicine plays a pivotal role in this context. Imaging modalities such as single-photon emission computed tomography (SPECT) enable the early identification of functional abnormalities through the use of targeted radiotracers that specifically localize inflammatory processes. In this regard, antibiotic-loaded nanoparticles have emerged as a promising platform for inflammation imaging, integrating diagnostic capabilities with potential therapeutic functionality. Among these systems, chitosan-based nanocarriers (CS-NPs), a nano-polymeric pharmaceutical excipient, were employed for the encapsulation of the antibiotic cefadroxil (CDX). The formulation was prepared via a simple ionic gelation (cross-linking) technique. The physicochemical properties of the resulting nanoparticles were characterized using transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), zeta potential analysis, and X-ray diffraction (XRD). Drug encapsulation efficiency and loading capacity were subsequently quantified by UV-visible spectrophotometry. For imaging applications, CDX-loaded CS-NPs (400 µg) were radiolabeled with technetium-99m in the presence of stannous chloride (50 µg) as a reducing agent, yielding a complex with a radiochemical efficiency of 94 ± 1.3%. The resulting 99mTc-CDX-CS-NPs demonstrated excellent in vitro stability in fresh serum for up to 6 hours, which is suitable for diagnostic imaging applications. In vivo biodistribution studies in murine models of both septic and aseptic inflammation revealed significant tracer accumulation at infected and inflamed sites, with high target-to-non-target (T/NT) ratios of 8.55 and 6.02 after 2 hours post-injection, respectively. These findings suggest the developed radiotracer's ability to effectually localize septic and aseptic foci, irrespective of their underlying etiology.