Evaluating chronic bone and soft tissue infections with [68Ga]Ga-Pentixafor PET/CT: a head-to-head comparison with scintigraphy

Abstract Purpose Chronic bone and soft tissue infections pose a diagnostic challenge, as conventional imaging techniques often show limited sensitivity and specificity. Given that CXCR4 chemokine receptors are expressed on lymphocytes, key mediators of chronic inflammatory response, we hypothesized that CXCR4-targeted imaging may offer enhanced diagnostic accuracy. Accordingly, this study aimed to evaluate the diagnostic performance of [ 68 Ga]Ga-Pentixafor PET/CT in comparison with conventional 3-phase bone scintigraphy and [ 99m Tc]Tc-HMPAO-labelled leucocyte scintigraphy in patients with suspected chronic bone and soft tissue infections. Methods In this retrospective single-centre study, we included patients who underwent both conventional scintigraphic imaging and [ 68 Ga]Ga-Pentixafor PET/CT. Asymptomatic prostheses, orthopaedic implants, and diabetic foot regions within the same cohort served as controls. Two nuclear medicine specialists, blinded to patient data, evaluated imaging findings in consensus visually and quantitatively. Final diagnoses were confirmed by microbiological culture and/or histopathology for infected sites, and by clinical and radiological follow-up for non-infected control sites. Results A total of 20 patients with 25 suspected infectious foci and 14 control sites were evaluated. Of the 25 sites, 21 were confirmed to be infected; no infections were observed in the control sites. Scintigraphy correctly identified 19 infection sites (sensitivity: 90%, specificity: 83%), while [ 68 Ga]Ga-Pentixafor PET/CT was positive in all 21 infection sites, but demonstrated two false-positives (sensitivity: 100%, specificity: 89%). PET/CT showed higher overall accuracy (95% vs. 87%), although this difference did not reach statistical significance ( p = 0.07). Conclusion [ 68 Ga]Ga-Pentixafor PET/CT was accurate in detecting BSTIs, suggesting potential utility as a single-scan imaging approach. These results align with findings from limited prior studies and underscore the need for validation in larger cohorts.