Meta-Analysis

. 2025 Sep;52(11):3975-3989.

doi: 10.1007/s00259-025-07277-0. Epub 2025 Apr 25.

Head-to-head comparison of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and [¹⁸F]FDG in gynaecological malignancies: systematic literature review and meta-analysis

Anita Florit^{1

2}, Elizabeth J de Koster^{3

4}, Serena Sassano⁵, Lejla Alic⁶, Giusi Pisano⁵, Floris H P van Velden⁴, Salvatore Annunziata¹, Irina Primac⁷, Maria Rosaria Ruggiero⁸, Cristina Müller^{9

10}, Evis Sala^{11

12}, Wolfgang P Fendler¹³, Giovanni Scambia^{14

15}, Lioe-Fee de Geus-Oei^{2

4

16}, Anna Fagotti^{14

15}, Vittoria Rufini^{17

18}, Angela Collarino¹

Affiliations

¹ Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.
² Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.
³ Department of Surgery, Haaglanden Medical Centre, The Hague, The Netherlands.
⁴ Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
⁵ Section of Nuclear Medicine, Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Magnetic Detection & Imaging Group, Technical Medical Centre, University of Twente, Enschede, The Netherlands.
⁷ Radiobiology Unit, Nuclear Medical Applications Institute, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium.
⁸ PET/CT Centre, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
⁹ Centre for Radiopharmaceutical Sciences, PSI Center for Life Sciences, Villigen-PSI, Switzerland.
¹⁰ Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
¹¹ Section of Radiology, University Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Advanced Radiodiagnostics Centre, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹³ Department of Nuclear Medicine, DKTK and NCT University Hospital Essen, Essen, Germany.
¹⁴ Gynaecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹⁵ Section of Obstetrics and Gynaecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy.
¹⁶ Department of Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.
¹⁷ Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy. vittoria.rufini@unicatt.it.
¹⁸ Section of Nuclear Medicine, Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy. vittoria.rufini@unicatt.it.

PMID: 40278857
PMCID: PMC12397109
DOI: 10.1007/s00259-025-07277-0

Meta-Analysis

Head-to-head comparison of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and [¹⁸F]FDG in gynaecological malignancies: systematic literature review and meta-analysis

Anita Florit et al. Eur J Nucl Med Mol Imaging. 2025 Sep.

. 2025 Sep;52(11):3975-3989.

doi: 10.1007/s00259-025-07277-0. Epub 2025 Apr 25.

Authors

Affiliations

¹ Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy.
² Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.
³ Department of Surgery, Haaglanden Medical Centre, The Hague, The Netherlands.
⁴ Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
⁵ Section of Nuclear Medicine, Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy.
⁶ Magnetic Detection & Imaging Group, Technical Medical Centre, University of Twente, Enschede, The Netherlands.
⁷ Radiobiology Unit, Nuclear Medical Applications Institute, Belgian Nuclear Research Centre (SCK CEN), Mol, Belgium.
⁸ PET/CT Centre, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
⁹ Centre for Radiopharmaceutical Sciences, PSI Center for Life Sciences, Villigen-PSI, Switzerland.
¹⁰ Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
¹¹ Section of Radiology, University Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Advanced Radiodiagnostics Centre, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹³ Department of Nuclear Medicine, DKTK and NCT University Hospital Essen, Essen, Germany.
¹⁴ Gynaecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
¹⁵ Section of Obstetrics and Gynaecology, University Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy.
¹⁶ Department of Radiation Science and Technology, Delft University of Technology, Delft, The Netherlands.
¹⁷ Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli, 8, 00168, Rome, Italy. vittoria.rufini@unicatt.it.
¹⁸ Section of Nuclear Medicine, Department of Radiological Sciences and Haematology, Università Cattolica del Sacro Cuore, Rome, Italy. vittoria.rufini@unicatt.it.

PMID: 40278857
PMCID: PMC12397109
DOI: 10.1007/s00259-025-07277-0

Abstract

Purpose: This study aims to systematically review and perform a meta-analysis to compare the diagnostic performance of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) in gynaecological cancers.

Methods: A comprehensive search of PubMed/MEDLINE and EMBASE was conducted and updated to October 25, 2024, to identify clinical studies evaluating FAPI and [¹⁸F]FDG PET/CT or PET/MR in patients with gynaecological cancer. Quality was assessed using the QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies). Per-lesion pooled estimates of sensitivity, specificity, positive predictive value, and negative predictive value were calculated with 95% confidence intervals.

Results: Ten studies were included for qualitative assessment and five studies focusing on ovarian cancer were included in the meta-analysis. The detection rates of primary cervical cancer ranged from 96 to 100% for both radiopharmaceuticals. For the primary tumour in ovarian cancer, the pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 95% and 92%, and the pooled specificities were 81% for both radiopharmaceuticals. Nodal metastases detection was higher with ⁶⁸Ga-FAPI compared with [¹⁸F]FDG in cervical cancer. Similarly, in ovarian cancer the estimated pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 97% and 88%, and the pooled specificities were 83% and 41%, respectively. At peritoneal metastases analysis in ovarian cancer, the pooled sensitivities of ⁶⁸Ga-FAPI and [¹⁸F]FDG were 97% and 70%, and the pooled specificities were 93% and 88%, respectively. At the visual assessment of peritoneal cancer scores, such as peritoneal cancer index, ⁶⁸Ga-FAPI detected a greater tumour burden compared with [¹⁸F]FDG. A comparative analysis of the PET semiquantitative parameters was also performed.

Conclusion: Despite limited literature data, radiopharmaceuticals based on FAPIs are a promising alternative to [¹⁸F]FDG for imaging gynaecological cancers, in particular for the detection of nodal metastases in cervical and ovarian cancers, as well as for detecting peritoneal metastases in ovarian cancers. Larger prospective studies are needed to confirm these results and promote the inclusion of FAPI radiopharmaceuticals in clinical practice.

Clinical trial number: Not applicable.

Keywords: FAPI; Gynaecological cancers; Meta-analysis; PET/CT; Systematic review; [18F]FDG.

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Conflict of interest statement

Declarations. Ethics and consent to participate: Not applicable. Conflict of interests: W.P.F. reports fees from SOFIE Bioscience (research funding), Janssen (consultant, speaker), Perceptive (consultant, image review), Bayer (consultant, speaker, research funding), Novartis (speaker, consultant), Telix (speaker), GE Healthcare (speaker, consultant), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), Urotrials (speaker), Lilly (consultant) outside of the submitted work. The rest of the authors report that they have no conflict of interest.

Figures

**Fig. 1**
Literature search and study selection

**Fig. 2**
Per-lesion analysis of the nodal metastases in ovarian cancer. (A) ⁶⁸Ga-FAPI sensitivity; (B) [¹⁸F]FDG sensitivity; (C) ⁶⁸Ga-FAPI specificity; (D) [¹⁸F]FDG specificity; (E) ⁶⁸Ga-FAPI positive predictive value (PPV); (F) [¹⁸F]FDG PPV; (G) ⁶⁸Ga-FAPI negative predictive value (NPV); (H) [¹⁸F]FDG NPV

**Fig. 3**
Per-lesion analysis of the peritoneal metastases in ovarian cancer. (A) ⁶⁸Ga-FAPI sensitivity; (B) [¹⁸F]FDG sensitivity; (C) ⁶⁸Ga-FAPI specificity; (D) [¹⁸F]FDG specificity; (E) ⁶⁸Ga-FAPI positive predictive value (PPV); (F) [¹⁸F]FDG PPV; (G) ⁶⁸Ga-FAPI negative predictive value (NPV); (H) [¹⁸F]FDG NPV

See this image and copyright information in PMC

References

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Head-to-head comparison of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and [¹⁸F]FDG in gynaecological malignancies: systematic literature review and meta-analysis

Affiliations

Head-to-head comparison of fibroblast activation protein inhibitors (FAPI) radiopharmaceuticals and [¹⁸F]FDG in gynaecological malignancies: systematic literature review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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