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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 03-02-2022 | Computed Tomography | Original Article

Head-to-head evaluation of [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma

Authors: Bingxin Gu, Xin Liu, Shuoer Wang, Xiaoping Xu, Xiaosheng Liu, Silong Hu, Wangjun Yan, Zhiguo Luo, Shaoli Song

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2022

Abstract

Purpose

We aimed to evaluate the value of [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT for the diagnosis of recurrent soft tissue sarcoma (STS), compared with [¹⁸F]FDG PET/CT.

Methods

A total of 45 patients (21 females and 24 males; median age, 46 years; range, 18–71 years) with 13 subtypes of STS underwent [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT examination within 1 week for assessment local relapse or distant metastasis. Positive lesions on PET/CT images were verified by biopsy or 3-month follow-up. Wilcoxon matched-pairs signed-rank test was used to compare the semiquantitative values (SUV_max and TBR) of [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 in tumor lesions, and McNemar test was applied to test for differences of both tracers.

Results

Among the 45 patients, 282 local relapses and distant metastases were identified. Compared to [¹⁸F]FDG, [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT detected more lesions (275 vs. 186) and outperformed in sensitivity, specificity, PPV, NPV, and accuracy for the diagnosis of recurrent lesions (P < 0.001). [⁶⁸ Ga]Ga-DOTA-FAPI-04 demonstrated significantly higher values of SUV_max and TBR than [¹⁸F]FDG PET/CT in liposarcoma (P = 0.011 and P < 0.001, respectively), malignant solitary fibrous tumor (MSFT) (P < 0.001 and P < 0.001, respectively), and interdigitating dendritic cell sarcoma (IDCS) (P < 0.001and P < 0.001, respectively). While mean SUV_max and TBR presented favorable uptake of [¹⁸F]FDG over [⁶⁸ Ga]Ga-DOTA-FAPI-04 in undifferentiated pleomorphic sarcoma (UPS) (P = 0.003 and P < 0.001, respectively) and rhabdomyosarcoma (RMS) (P < 0.001 and P < 0.001, respectively).

Conclusion

[⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT is a promising new imaging modality for recurrent surveillance of STS, and compares favorably with [¹⁸F]FDG for identifying recurrent lesions of liposarcoma, MSFT, and IDCS.

Available only for authorised users

WHO Classification of Tumors Editorial Board. WHO classification of tumours of soft tissue and bone. 5th ed. Lyon, France: IARC Press; 2020.

Comandone A, Petrelli F, Boglione A, Barni S. Salvage therapy in advanced adult soft tissue sarcoma: a systematic review and meta-analysis of randomized trials. Oncologist. 2017;22(12):1518–27. https://doi.org/10.1634/theoncologist.2016-0474.CrossRefPubMedPubMedCentral

Gamboa AC, Gronchi A, Cardona K. Soft-tissue sarcoma in adults: an update on the current state of histiotype-specific management in an era of personalized medicine. CA Cancer J Clin. 2020;70(3):200–29. https://doi.org/10.3322/caac.21605.CrossRefPubMed

Macpherson RE, Pratap S, Tyrrell H, Khonsari M, Wilson S, Gibbons M, et al. Retrospective audit of 957 consecutive (18)F-FDG PET-CT scans compared to CT and MRI in 493 patients with different histological subtypes of bone and soft tissue sarcoma. Clin Sarcoma Res. 2018;8:9. https://doi.org/10.1186/s13569-018-0095-9.CrossRefPubMedPubMedCentral

Ha SC, Oh JS, Roh JL, Moon H, Kim JS, Cho KJ, et al. Pretreatment tumor SUVmax predicts disease-specific and overall survival in patients with head and neck soft tissue sarcoma. Eur J Nucl Med Mol Imaging. 2017;44(1):33–40. https://doi.org/10.1007/s00259-016-3456-8.CrossRefPubMed

Salaün PY, Abgral R, Malard O, Querellou-Lefranc S, Quere G, Wartski M, et al. Good clinical practice recommendations for the use of PET/CT in oncology. Eur J Nucl Med Mol Imaging. 2020;47(1):28–50. https://doi.org/10.1007/s00259-019-04553-8.CrossRefPubMed

Noebauer-Huhmann IM, Weber MA, Lalam RK, Trattnig S, Bohndorf K, Vanhoenacker F, et al. Soft tissue tumors in adults: ESSR-approved guidelines for diagnostic imaging. Semin Musculoskelet Radiol. 2015;19(5):475–82. https://doi.org/10.1055/s-0035-1569251.CrossRefPubMed

Benz MR, Crompton JG, Harder D. PET/CT variants and pitfalls in bone and soft tissue sarcoma. Semin Nucl Med. 2021;51(6):584–92. https://doi.org/10.1053/j.semnuclmed.2021.06.009.CrossRefPubMed

Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. (68)Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. 2019;60(6):801–5. https://doi.org/10.2967/jnumed.119.227967.CrossRefPubMedPubMedCentral

10.

Koczorowska MM, Tholen S, Bucher F, Lutz L, Kizhakkedathu JN, De Wever O, et al. Fibroblast activation protein-alpha, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations. Mol Oncol. 2016;10(1):40–58. https://doi.org/10.1016/j.molonc.2015.08.001.CrossRefPubMed

11.

Scanlan MJ, Raj BK, Calvo B, Garin-Chesa P, Sanz-Moncasi MP, Healey JH, et al. Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblasts of epithelial cancers. Proc Natl Acad Sci USA. 1994;91(12):5657–61. https://doi.org/10.1073/pnas.91.12.5657.CrossRefPubMedPubMedCentral

12.

Rettig WJ, Garin-Chesa P, Beresford HR, Oettgen HF, Melamed MR, Old LJ. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells. Proc Natl Acad Sci USA. 1988;85(9):3110–4. https://doi.org/10.1073/pnas.85.9.3110.CrossRefPubMedPubMedCentral

13.

Dohi O, Ohtani H, Hatori M, Sato E, Hosaka M, Nagura H, et al. Histogenesis-specific expression of fibroblast activation protein and dipeptidylpeptidase-IV in human bone and soft tissue tumours. Histopathology. 2009;55(4):432–40. https://doi.org/10.1111/j.1365-2559.2009.03399.x.CrossRefPubMedPubMedCentral

14.

Lindner T, Loktev A, Altmann A, Giesel F, Kratochwil C, Debus J, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. 2018;59(9):1415–22. https://doi.org/10.2967/jnumed.118.210443.CrossRefPubMed

15.

Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [(68)Ga]Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [(18)F]FDG PET/CT findings. Eur J Nucl Med Mol Imaging. 2021;48(1):73–86. https://doi.org/10.1007/s00259-020-04940-6.CrossRefPubMed

16.

Chen H, Pang Y, Wu J, Zhao L, Hao B, Wu J, et al. Comparison of [(68)Ga]Ga-DOTA-FAPI-04 and [(18)F] 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(8):1820–32. https://doi.org/10.1007/s00259-020-04769-z.CrossRefPubMed

17.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

18.

Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81–94. https://doi.org/10.1038/nrclinonc.2017.166.CrossRefPubMed

19.

Lee JW, Park JY, Lee HJ, Lee JJ, Moon SH, Kang SY, et al. Preoperative [(18)F]FDG PET/CT tumour heterogeneity index in patients with uterine leiomyosarcoma: a multicentre retrospective study. Eur J Nucl Med Mol Imaging. 2018;45(8):1309–16. https://doi.org/10.1007/s00259-018-3975-6.CrossRefPubMed

20.

Annovazzi A, Ferraresi V, Anelli V, Covello R, Vari S, Zoccali C, et al. [(18)F]FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma. Eur Radiol. 2021;31(9):7012–21. https://doi.org/10.1007/s00330-021-07841-w.CrossRefPubMed

21.

Charest M, Hickeson M, Lisbona R, Novales-Diaz JA, Derbekyan V, Turcotte RE. FDG PET/CT imaging in primary osseous and soft tissue sarcomas: a retrospective review of 212 cases. Eur J Nucl Med Mol Imaging. 2009;36(12):1944–51. https://doi.org/10.1007/s00259-009-1203-0.CrossRefPubMed

22.

Lim HJ, Johnny Ong CA, Tan JW, Ching Teo MC. Utility of positron emission tomography/computed tomography (PET/CT) imaging in the evaluation of sarcomas: a systematic review. Crit Rev Oncol Hematol. 2019;143:1–13. https://doi.org/10.1016/j.critrevonc.2019.07.002.CrossRefPubMed

23.

Erfanian Y, Grueneisen J, Kirchner J, Wetter A, Podleska LE, Bauer S, et al. Integrated ¹⁸F-FDG PET/MRI compared to MRI alone for identification of local recurrences of soft tissue sarcomas: a comparison trial. Eur J Nucl Med Mol Imaging. 2017;44(11):1823–31. https://doi.org/10.1007/s00259-017-3736-y.CrossRefPubMed

24.

Kessler L, Ferdinandus J, Hirmas N, Bauer S, Dirksen U, Zarrad F, et al. Ga-68-FAPI as diagnostic tool in sarcoma: data from the FAPI-PET prospective observational trial. J Nucl Med. 2022;63(1):89–95. https://doi.org/10.2967/jnumed.121.262096.CrossRefPubMed

25.

Koerber SA, Finck R, Dendl K, Uhl M, Lindner T, Kratochwil C, et al. Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT. Eur J Nucl Med Mol Imaging. 2021;48(12):3918–24. https://doi.org/10.1007/s00259-021-05374-4.CrossRefPubMedPubMedCentral

26.

Dendl K, Koerber SA, Kratochwil C, Cardinale J, Finck R, Dabir M, et al. FAP and FAPI-PET/CT in malignant and non-malignant diseases: a perfect symbiosis? Cancers (Basel). 2021;13(19):4946. https://doi.org/10.3390/cancers13194946.CrossRef

27.

Kessler L, Ferdinandus J, Hirmas N, Zarrad F, Nader M, Kersting D, et al. Pitfalls and common findings in (68)Ga-FAPI-PET - a pictorial analysis. J Nucl Med. 2021. https://doi.org/10.2967/jnumed.121.262808.CrossRefPubMed

28.

Qin C, Song Y, Liu X, Gai Y, Liu Q, Ruan W, et al. Increased uptake of (68)Ga-DOTA-FAPI-04 in bones and joints: metastases and beyond. Eur J Nucl Med Mol Imaging. 2021. https://doi.org/10.1007/s00259-021-05472-3.CrossRefPubMedPubMedCentral

29.

Syed M, Flechsig P, Liermann J, Windisch P, Staudinger F, Akbaba S, et al. Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers. Eur J Nucl Med Mol Imaging. 2020;47(12):2836–45. https://doi.org/10.1007/s00259-020-04859-y.CrossRefPubMedPubMedCentral

30.

Shi X, Xing H, Yang X, Li F, Yao S, Zhang H, et al. Fibroblast imaging of hepatic carcinoma with (68)Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules. Eur J Nucl Med Mol Imaging. 2021;48(1):196–203. https://doi.org/10.1007/s00259-020-04882-z.CrossRefPubMed

31.

Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of (68)Ga-FAPI and (18)F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021;298(2):393–402. https://doi.org/10.1148/radiol.2020203275.CrossRefPubMed

32.

Ding F, Huang C, Liang C, Wang C, Liu J, Tang D. (68)Ga-FAPI-04 vs. (18)F-FDG in a longitudinal preclinical PET imaging of metastatic breast cancer. Eur J Nucl Med Mol Imaging. 2021;49(1):290–300. https://doi.org/10.1007/s00259-021-05442-9.

33.

Frezza AM, Stacchiotti S, Gronchi A. Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new. BMC Med. 2017;15(1):109. https://doi.org/10.1186/s12916-017-0872-y.CrossRefPubMedPubMedCentral

34.

Kratochwil C, Giesel FL, Rathke H, Fink R, Dendl K, Debus J, et al. [(153)Sm]Samarium-labeled FAPI-46 radioligand therapy in a patient with lung metastases of a sarcoma. Eur J Nucl Med Mol Imaging. 2021;48(9):3011–3. https://doi.org/10.1007/s00259-021-05273-8.CrossRefPubMedPubMedCentral

35.

Ferdinandus J, Fragoso Costa P, Kessler L, Weber M, Hirmas N, Kostbade K, et al. Initial clinical experience with (90)Y-FAPI-46 radioligand therapy for advanced stage solid tumors: a case series of nine patients. J Nucl Med. 2021. https://doi.org/10.2967/jnumed.121.262468.CrossRefPubMedPubMedCentral

Title: Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma
Authors: Bingxin Gu
Xin Liu
Shuoer Wang
Xiaoping Xu
Xiaosheng Liu
Silong Hu
Wangjun Yan
Zhiguo Luo
Shaoli Song
Publication date: 03-02-2022
Publisher: Springer Berlin Heidelberg
Keywords: Computed Tomography
Metastasis
Liposarcoma
Rhabdomyosarcoma
Computed Tomography
Soft Tissue Sarcoma
Sarcoma
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05700-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Head-to-head evaluation of [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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