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Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers

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Abstract

Purpose

In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [18F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT in patients with RAI-R-FCTC.

Methods

In this retrospective study, a total of 117 patients with RAI-R-FCTC were included. The study population consisted of 68 females and 49 males, with a mean age of 53.2 ± 11.7 years. The aim of the study was to perform a comprehensive qualitative and quantitative assessment of [68Ga]Ga-DOTA.SA.FAPi and [18F]F-FDG PET/CT scans in RAI-R-FCTC patients. The qualitative assessment involved comparing patient-based and lesion-based visual interpretations of both scans, while the quantitative assessment included analyzing standardized uptake values corrected for lean body mass (SULpeak and SULavg). The findings obtained from the scans were validated by correlating them with morphological findings from diagnostic computed tomography and/or histopathological examination.

Results

Among the 117 RAI-R-FCTC patients, 60 had unilateral local disease, and 9 had bilateral lesions with complete concordance in the detection rate on both PET scans. [68Ga]Ga-DOTA.SA.FAPi had a higher detection rate for lymph nodes (95.4% vs 86.6%, p<0.0001), liver metastases (100% vs. 81.3%, p<0.0001), and brain metastases (100% vs. 39%, p<0.0001) compared to [18F]F-FDG. The detection rates for pleural and bone metastases were similar between the two radiotracers. For lung metastases, [68Ga]Ga-DOTA.SA.FAPi showed a detection rate of 81.7%, whereas [18F]F-FDG had a detection rate of 64.6%. Remarkably, [68Ga]Ga-DOTA.SA.FAPi was able to detect a bowel metastasis that was missed on [18F]F-FDG scan. The median standardized uptake values (SUL) were generally comparable between the two radiotracers, except for brain metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 13.9 vs. 6.7, p-0.0001) and muscle metastases (SULpeak [68Ga]Ga-DOTA.SA.FAPi vs. [18F]F-FDG: 9.56 vs. 5.62, p-0.0085), where [68Ga]Ga-DOTA.SA.FAPi exhibited higher uptake.

Conclusion

The study results demonstrate the superior performance of [68Ga]Ga-DOTA.SA.FAPi compared to [18F]F-FDG PET/CT in detecting lymph nodal, liver, bowel, and brain metastases in patients with RAI-R-FCTC. These findings highlight the potential of [68Ga]Ga-DOTA.SA.FAPi as a theranostic tool that can complement the benefits of [18F]F-FDG PET/CT in the imaging of RAI-R-FCTC.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Zarnegar R, Brunaud L, Kanauchi H, et al. Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using trichostatin A, a histone deacetylase inhibitor. Surgery. 2002;132:984–90.

    Article  PubMed  Google Scholar 

  2. Dralle H, Machens A, Basa J, Fatourechi V, Franceschi S, Hay ID, et al. Follicular cell-derived thyroid cancer. Nat Rev Dis Primers. 2015;10(1):15077.

    Article  Google Scholar 

  3. Worden F. Treatment strategies for radioactive iodine refractory differentiated thyroid cancer. Ther Adv Med Oncol. 2014;6:267–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 2013;381:1058–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Choudhury PS, Gupta M. Differentiated thyroid cancer theranostics: radioiodine and beyond. Br J Radiol. 2018;91:20180136.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Deandreis D, GhuzlanA Al, Leboulleux S, et al. Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome? Endocr Relat Cancer. 2011;18:159–69.

    Article  CAS  PubMed  Google Scholar 

  7. Rosenbaum-KrummeSJ GR, Bockisch A, et al. 18F-FDG PET/CT changes therapy management in high-risk DTC after first radioiodine therapy. Eur J Nucl Med Mol Imaging. 2012;39:1373–80.

    Article  Google Scholar 

  8. Grewal RK, HoA SH. Novel approaches to thyroid cancer treatment and response assessment. Semin Nucl Med. 2016;46:109–18.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Klain M, Zampella E, Nappi C, et al. Advances in functional imaging of differentiated thyroid cancer. Cancers. 2021;13:4748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Boellaard R, Delgado-Bolton R, Oyen WJ, et al. European Association of Nuclear Medicine (EANM) FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54.

    Article  CAS  PubMed  Google Scholar 

  11. Fozzatti L, Cheng SY. Tumor cells and cancer-associated fibroblasts: a synergistic crosstalk to promote thyroid cancer. Endocrinol Metab (Seoul). 2020;35:673–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cho JG, Byeon HK, Oh KH, et al. Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis. Eur Arch Otorhinolaryngol. 2018;275:2355–61.

    Article  PubMed  Google Scholar 

  13. Sun WY, Jung WH, Koo JS. 2016. Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma.Tumour Biol. 37:8197-8207.

  14. Jansen K, Heirbaut L, Verkerk R, et al. Extended structure-activity relationship and pharmacokinetic investigation of (4-quinolinoyl)glycyl-2-cyanopyrrolidine inhibitors of fibroblast activation protein (FAP). J Med Chem. 2014;57:3053–74.

    Article  CAS  PubMed  Google Scholar 

  15. Giesel FL, Kratochwil C, Lindner T, et al. 68Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. J Nucl Med. 2019;60:386–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kratochwil C, Flechsig P, Lindner T, et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60:801–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Meyer C, Dahlbom M, Lindner T, et al. Radiation dosimetry and biodistribution of 68Ga-FAPI-46 PET imaging in cancer patients. J Nucl Med. 2020;61:1171–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ballal S, Yadav MP, Moon ES, et al. Biodistribution, pharmacokinetics, dosimetry of [68Ga]GaDOTA.SA.FAPi, and the head-to-head comparison with[18F]F-FDG PET/CT in patients with various cancers. Eur J Nucl Med Mol Imaging. 2021;48:1915–31.

    Article  CAS  PubMed  Google Scholar 

  19. Moon ES, Ballal S, Yadav MP, et al. Fibroblast activation protein (FAP) targeting homodimeric FAP inhibitor radiotheranostics: a step to improve tumor uptake and retention time. Am J Nucl Med Mol Imaging. 2021;11:476–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Pang Y, Zhao L, Luo Z, et al. Comparison of 68Ga-FAPI and 18F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298:393–402.

    Article  PubMed  Google Scholar 

  21. Chen H, Pang Y, Wu J, et al. Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur J Nucl Med Mol Imaging. 2020;47:1820–32.

    Article  PubMed  Google Scholar 

  22. Wang L, Tang G, Hu K, et al. Comparison of 68Ga-FAPI and 18F-FDG PET/CT in the evaluation of advanced lung cancer. Radiology. 2022;303:191–9.

    Article  PubMed  Google Scholar 

  23. Treglia G, Muoio B, Roustaei H, Kiamanesh Z, Aryana K, Sadeghi R. Head-to-head comparison of fibroblast activation protein inhibitors (FAPI) radiotracers versus [18F]F-FDG in oncology: a systematic review. Int J Mol Sci. 2021;22:11192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rivera M, Ghossein Ronald A, et al. Histopathologic characterization of radioactive iodine-refractory fluorodeoxyglucose-positron emission tomography-positive thyroid carcinoma. Cancer. 2008;113:48–56.

    Article  PubMed  Google Scholar 

  25. Huang R, Pu Y, Huang S, et al. FAPI-PET/CT in cancer imaging: a potential novel molecule of the century. Front Oncol. 2022;12:854658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ballal S, Yadav MP, Roesch F, Raju S, Satapathy S, Sheokand P, Moon ES, Martin M, Agarwal S, Tripathi M, Bal C. 2023. Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC PET/CT imaging for the follow-up surveillance of patients with medullary thyroid cancer. Thyroid. 2023 May 12. https://doi.org/10.1089/thy.2023.0008

  27. Ballal S, Yadav MP, Moon ES, et al. Novel fibroblast activation protein inhibitor-based targeted theranostics for radioiodine-refractory differentiated thyroid cancer patients: a pilot study. Thyroid. 2022;32:65–77.

    CAS  PubMed  Google Scholar 

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Author notes

  1. Sanjana Ballal and Madhav P. Yadav contributed equally in the making of this manuscript.

Authors and Affiliations

  1. Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India

    Sanjana Ballal, Madhav P. Yadav, Swayamjeet Satapathy, Nicky Wakade, Parvind Sheokand, Madhavi Tripathi, Kunal R. Chandekar & Chandrasekhar Bal

  2. Department of Chemistry, Johannes Gutenberg University, Mainz, Germany

    Frank Roesch, Euy Sung Moon & Marcel Martin

  3. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

    Shipra Agarwal

  4. Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

    Ranjit Kumar Sahoo & Sameer Rastogi

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  1. Sanjana Ballal
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Contributions

The study’s conception and design involved contributions from all authors. Sanjana Ballal, Madhav Prasad Yadav, Nicky Wakade, Parvind Sheokand, Swayamjeet Satapathy, and Kunal R. Chandekar were responsible for material preparation, data collection, and analysis. The initial draft of the manuscript was written by Sanjana Ballal and Madhav Prasad Yadav. Chandrasekhar Bal and Madhavi Tripathi processed and reported the images, while Shipra Agarwal reviewed the pathology reports. Dr. Ranjit Kumar Sahoo and Dr. Sameer Rastogi referred patients for scans. Our collaborators from the University of Mainz, Frank Roesch, Euy Sung Moon, and Marcel Martin, synthesized the precursor and provided valuable input to finalize the manuscript. All authors provided feedback on earlier versions of the manuscript and approved the final version.

Corresponding author

Correspondence to Chandrasekhar Bal.

Ethics declarations

Ethical approval

Ethical clearance received Ref No: IECPG:22/27

Consent to participate

Written informed consent was obtained from all patients to participate in the study, use clinical information to analyze data, and use images for the purpose of publication.

Conflict of interest

The authors declare no competing interests.

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A section of this project was released as a pre-print on Research Square. Sanjana Ballal, Madhav Yadav, Nicky Wakade et al. Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers, 06 February 2023, PREPRINT (version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-2382675/v1].

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Ballal, S., Yadav, M.P., Roesch, F. et al. Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers. Eur J Nucl Med Mol Imaging 51, 233–244 (2023). https://doi.org/10.1007/s00259-023-06404-z

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