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State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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The manuscript represents valid work, and neither this manuscript nor one with substantially similar content under the same authorship has been published or is being considered for publication elsewhere.

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Acknowledgements

We thank Prof. Stefanos Bonovas for his support in the meta-analysis command.

Funding

M. Sollini is supported by the Investigator Grant 2019–23596, funded by AIRC (Italian Association for Cancer Research) won by AC.

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MS, MK and AC conceptualised the project; FF performed literature search; MS, MK, and FF performed articles selection; FG, NG, MS performed the analyses and prepared the figures; NG, FG, FF, MS, MK interpreted the analyses results; MS, FF and MK drafted the paper; NG, FG, and AC critically commented the paper; all the authors critically revised the paper and approved the submitted version of the manuscript.

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Correspondence to Fabrizia Gelardi.

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Prof. Chiti reports a fellowship grant from Sanofi, personal fees from AAA, Blue Earth Diagnostics and General Electric Healthcare, outside the submitted work. The other authors do not report any conflict of interest.

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Sollini, M., Kirienko, M., Gelardi, F. et al. State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 48, 4396–4414 (2021). https://doi.org/10.1007/s00259-021-05475-0

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