Radiolabeling, characterization, and bioevaluation of <sup>99m</sup>Tc-Itaconic acid for detection of inflammation in mice.

Abstract

Itaconic acid (ITA), a naturally occurring dicarboxylic acid, demonstrates potent antibacterial and anti-inflammatory activity. Differentiating bacterial infections from sterile inflammation remains a significant clinical challenge, necessitating the development of specific diagnostic radiopharmaceuticals. This research presents the radiolabeling of ITA with technetium-99m (99mTc) and evaluates its potential as an infection-targeted tracer. The 99mTc-ITA complex was synthesized using sodium dithionite under optimized conditions (0.5 mg ITA, 20 mg Na2S2O4, pH 6.0, 30 min, 25 °C) and the structure of ITA was confirmed by FTIR, SEM, and XRD. The radiochemical yield reached 95.4 ± 0.2 %, with excellent stability in saline and serum for 24 h. Antibacterial assays confirmed preserved biological activity: unlabeled ITA produced a 30 mm inhibition zone against Staphylococcus aureus, while the radiolabeled ITA retained strong bacterial binding (74 ± 0.54 % at 120 min). Biodistribution studies in Swiss Albino mice demonstrated rapid clearance, predominant renal excretion, and minimal nonspecific uptake. Notably, infection models showed high target specificity, achieving a peak target-to-non-target ratio of 5.8 at 2 h post-injection, compared with 1.85 in sterile inflammation. These findings establish 99mTc-ITA as a stable, biologically active, and infection-selective radiopharmaceutical, with promising utility for nuclear imaging applications, particularly for the reliable differentiation of bacterial infections from sterile inflammatory processes.