Martina Sollini1,2, Margarita Kirienko3, Fabrizia Gelardi4,5, Francesco Fiz2, Noemi Gozzi2, Arturo Chiti1,2. 1. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4Pieve Emanuele, 20090, Milan, Italy. 2. IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy. 3. Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133, Milan, Italy. 4. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4Pieve Emanuele, 20090, Milan, Italy. fabrizia.gelardi@cancercenter.humanitas.it. 5. IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy. fabrizia.gelardi@cancercenter.humanitas.it.
Abstract
INTRODUCTION: Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [68 Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI)-have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role. MATERIALS AND METHODS: The search, limited to January 1st, 2018-March 31st, 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", "FAPI", "PET/CT", "positron emission tomography", "fibroblast", "cancer-associated fibroblasts", "CAF", "molecular imaging", and "fibroblast imaging". Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA "metaprop" command. Between-study statistical heterogeneity was tested (I2-statistics). RESULTS: Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n = 2, 29 patients), abdominal malignancies (n = 6, 171 patients), various cancers (n = 2, 143 patients), and radiation treatment planning (n = 4, 56 patients) were included in the meta-analysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I2 = 88.56% and I2 = 97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I2 = 89.18% and I2 = 95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity. CONCLUSIONS: FAPI-PET appears promising, especially in imaging cancers unsuitable for [18F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its role, specifically to identify cancer types, non-oncological diseases, and clinical settings for its applications.
INTRODUCTION: Fibroblast activation protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [68 Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI)-have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role. MATERIALS AND METHODS: The search, limited to January 1st, 2018-March 31st, 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", "FAPI", "PET/CT", "positron emission tomography", "fibroblast", "cancer-associated fibroblasts", "CAF", "molecular imaging", and "fibroblast imaging". Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA "metaprop" command. Between-study statistical heterogeneity was tested (I2-statistics). RESULTS: Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n = 2, 29 patients), abdominal malignancies (n = 6, 171 patients), various cancers (n = 2, 143 patients), and radiation treatment planning (n = 4, 56 patients) were included in the meta-analysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I2 = 88.56% and I2 = 97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I2 = 89.18% and I2 = 95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity. CONCLUSIONS: FAPI-PET appears promising, especially in imaging cancers unsuitable for [18F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its role, specifically to identify cancer types, non-oncological diseases, and clinical settings for its applications.
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