99mTc-DTPA-Collagen Radiotracer for the Noninvasive Detection of Infective Endocarditis.

Abstract

Infective endocarditis (IE) represents a significant concern among hospital-acquired infections, frequently caused by the Gram-positive bacterium Staphylococcus aureus. Nuclear imaging is emerging as a noninvasive and precise diagnostic tool. However, the gold standard radiotracer [¹⁸F]-FDG cannot distinguish between infection and inflammation, resulting in false positives. Based on the presence of collagen-binding proteins in the cell wall of S. aureus, we propose the radiolabeling of collagen for its evaluation in IE animal models by single-photon emission computed tomography (SPECT) imaging. We radiolabeled rat tail collagen I using DTPA chelator and [^99mTc]NaTcO₄. Selectivity was evaluated in vitro using 3 Gram-positive bacteria, 1 Gram-negative bacteria and 1 yeast. In vivo SPECT/computed tomography (CT) imaging was conducted on 8 SD rat models of IE and 8 sterile sham model as controls. Ex vivo biodistribution and autoradiography were performed following imaging. Diagnosis of IE was confirmed through microbiological studies and H&E histopathology. [^99mTc]-DTPA-Collagen was synthesized successfully with a yield of 42.86 ± 6.35%, a purity of 95.84 ± 1.85% and a stability higher than 90% after 50 h postincubation. In vitro uptake demonstrated the selectivity for Gram-positive bacteria (63.85 ± 15.15%). Ex vivo analysis confirmed hepato-splenic excretion. In vivo SPECT/CT imaging revealed highly localized uptake within the aortic valve with a sensitivity of 62.5% and specificity of 87.5%. We successfully synthesized and characterized a new SPECT radiotracer based on [^99mTc]Tc-radiolabeled collagen. In vitro studies demonstrated the selectivity of the radiotracer for Gram-positive bacteria. In vivo SPECT/CT-based assessment in an IE model confirmed the potential of this approach to detect active IE.