ArticleAnnals of nuclear medicine2026
Head-to-head comparison of ⁶⁸Ga-FAPI and ¹⁸F-FDG PET/CT in intracranial space-occupying lesions.
Article in Annals of nuclear medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeIntracranial space-occupying lesions (SOL), including primary brain tumors, metastases, and inflammatory lesions, require accurate characterization for diagnosis and management. Although ¹⁸F-FDG PET/CT reflects tumor glucose metabolism, its performance in the brain is limited by high physiological uptake. ⁶⁸Ga-FAPI PET/CT targets fibroblast activation protein in the tumor microenvironment and may provide complementary biological information with improved lesion conspicuity. This study aimed to compare ⁶⁸Ga-FAPI and ¹⁸F-FDG PET/CT for the evaluation of intracranial SOL.
methodsThirty-five patients with 55 intracranial lesions underwent paired ⁶⁸Ga-FAPI and ¹⁸F-FDG PET/CT within a 7-day interval. Imaging findings were compared with histopathology (n = 9) and/or MRI (n = 46) as reference standards. Lesion detection rate, diagnostic performance, tumor-to-background ratio (TBR), and semi-quantitative uptake parameters normalized to lean body mass (SUL) were evaluated. Receiver operating characteristic (ROC) analyses were performed to assess the ability of each tracer to differentiate neoplastic from non-neoplastic lesions.
results⁶⁸Ga-FAPI PET/CT detected more lesions than ¹⁸F-FDG PET/CT (48/55, 87.3% vs. 36/55, 65.5%) and approached the detection rate of MRI (54/55, 98.2%). FAPI demonstrated higher sensitivity and accuracy, whereas FDG showed higher specificity. FAPI demonstrated a significantly higher tumor-to-background ratio (TBR) than FDG (median, 342.00 [IQR, 164.25-502.00] vs. 4.71 [IQR, 3.48-7.42]; Z = 5.07, p < 0.001) in paired analysis of 34 lesions with measurable uptake on both tracers. In primary tumors, FAPI detected all lesions (13/13), whereas FDG detected 9/13 lesions. ROC analysis showed comparable diagnostic performance for differentiating neoplastic from non-neoplastic lesions (AUC 0.794 for FAPI vs. 0.796 for FDG). Exploratory analysis in high-grade tumors (n = 5) suggested a potential association between higher FDG uptake and shorter overall survival.
conclusionIn this cohort, intracranial lesions were predominantly metastatic, with MRI showing the highest detection rate. Compared with ¹⁸F-FDG PET/CT, ⁶⁸Ga-FAPI PET/CT demonstrated higher lesion detection and tumor-to-background contrast, approaching MRI performance. These findings support a complementary role for ⁶⁸Ga-FAPI PET/CT alongside MRI and ¹⁸F-FDG PET/CT in selected intracranial lesions, particularly when lesion conspicuity is limited by the high physiological brain uptake of FDG.
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