Diagnostic Accuracy of [68Ga]GaNOTA-Ubiquicidin PET-CT for Differentiating Infections from Cancer in Oncology Practice: Preliminary Results from a Pilot Study.

Purpose: Ubiquicidin (UBI) is a natural antimicrobial peptide that has shown potential for targeting microbial pathogens in both in-vitro and human studies. Infections are common in patients with cancer and can mimic the appearance of primary neoplasms or metastatic lesions on Fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) imaging. This pilot study aimed to determine the diagnostic accuracy of Gallium-68-1,4,7-triazacyclononane-1,4,7 triacetic acid ([68Ga]GaNOTA)-UBI PET-CT for differentiating infective from neoplastic lesions. Methods: This was a prospective diagnostic accuracy study. Consecutive patients presenting with lesions identified on [18F]FDG PET-CT scans, which were equivocal for diagnosing malignancy and focal infection, were eligible for inclusion in the study. 30 selected patients who gave written informed consent underwent [68Ga]GaNOTA-UBI PET-CT for lesion characterization. The lesions were considered positive for infection if the uptake of [68Ga]GaNOTA-UBI in the lesion was higher than in the mediastinal blood pool. Biopsy and microbiological assay from the lesions and/or clinicoradiologic follow-up were the reference standard. Measures of diagnostic accuracy of [68Ga]GaNOTA-UBI PET-CT were computed based on patient-based analysis. The statistical analysis was performed with the statistical package SPSS Version 27.0 (Armonk, NY, USA: IBM Corp). A 2-tailed P value of < 0.05 was considered statistically significant. Results: According to the reference standard 21/30 (70%) patients were eventually diagnosed with infective lesions, 8/30 (26.7%) with neoplastic lesions and one patient with sterile inflammation. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of [68Ga]GaNOTA-UBI PET-CT were calculated as 52%, 78%, 85%, 41% and 60%, respectively. The maximum standardized uptake value (SUVmax) of infective lesions was not significantly different from malignant lesions; however, the mean of the ratios of lesional SUVmax to mediastinal blood pool SUVmax (SUVratio) of the former was significantly higher than that of latter (p = 0.042). The area under the curve (AUC) for SUVratio as a diagnostic parameter was 0.688 at an optimal cutoff value of 0.74. Good interrater agreement for the interpretation of [68Ga]GaNOTA-UBI PET-CT scans was achieved (Cohen's κ = 0.73). Conclusion: [68Ga]GaNOTA-UBI PET-CT shows only a moderate diagnostic accuracy for distinguishing infective from neoplastic lesions in oncology patients. A higher PPV however indicates its potential applicability as a confirmatory test for infection in patients with a higher clinical probability for the latter.