Abstract
Purpose
We evaluated the potential usefulness of [68Ga]Ga-DOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) for the diagnosis of primary and metastatic lesions in various types of cancer, compared with [18F] FDG PET/CT.
Methods
A total of 75 patients with various types of cancer underwent contemporaneous [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT either for an initial assessment or for recurrence detection. Tumour uptake was quantified by the maximum standard uptake value (SUVmax). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of [18F] FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT were calculated and compared to evaluate the diagnostic efficacy.
Results
The study cohort consisted of 75 patients (47 males and 28 females; median age, 61.5 years; age range, 32–85 years). Fifty-four patients with 12 different tumour entities underwent paired [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for initial assessment, while the other 21 patients underwent paired scans for recurrence detection. [68Ga]Ga-DOTA-FAPI-04 PET/CT was able to clearly identify 12 types of malignant tumours with favourable tumour-to-background contrast, which resulted in a higher detection rate of primary tumours than did [18F] FDG PET/CT (98.2% vs. 82.1%, P = 0.021). Meanwhile, [68Ga]Ga-DOTA-FAPI-04 PET/CT showed a better sensitivity than [18F] FDG PET/CT in the detection of lymph nodes (86.4% vs. 45.5%, P = 0.004) and bone and visceral metastases (83.8% vs. 59.5%, P = 0.004).
Conclusion
[68Ga]Ga-DOTA-FAPI-04 PET/CT showed a superior diagnostic efficacy than [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer, especially in identifying liver metastases, peritoneal carcinomatosis, and brain tumours.
Similar content being viewed by others
References
Garin-Chesa P, Old LJ, Rettig WJ. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A. 1990;1990(87):7235–9.
Hamson EJ, Keane FM, Tholen S, Schilling O, Gorrell MD. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl. 2014;8(5–6):454–63. https://doi.org/10.1002/prca.201300095.
Siveke JT. Fibroblast-activating protein: targeting the roots of the tumor microenvironment. J Nucl Med. 2018;59(9):1412–4. https://doi.org/10.2967/jnumed.118.214361.
Cohen SJ, Alpaugh RK, Palazzo I, Meropol NJ, Rogatko A, Xu Z, et al. Fibroblast activation protein and its relationship to clinical outcome in pancreatic adenocarcinoma. Pancreas. 2008;37(2):154–8. https://doi.org/10.1097/MPA.0b013e31816618ce.
Zhang Y, Tang H, Cai J, Zhang T, Guo J, Feng D, et al. Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 2011;303(1):47–55. https://doi.org/10.1016/j.canlet.2011.01.011.
Ju M-J, Qiu S-J, Fan J, Xiao Y-S, Gao Q, Zhou J, et al. Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection. Am J Clin Pathol. 2009;131(4):498–510.
Wikberg ML, Edin S, Lundberg IV, Biology BVGJT. High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumor Biol. 2013;34(2):1013–20.
Rettig WJ, Su SL, Fortunato SR, Scanlan MJ, Raj BKM, Garin-Chesa P, et al. Fibroblast activation protein: purification, epitope mapping and induction by growth factors. Int J Cancer. 1994;58(3):385–92.
Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jager D, et al. A tumor-imaging method targeting cancer-associated fibroblasts. J Nucl Med. 2018;59(9):1423–9. https://doi.org/10.2967/jnumed.118.210435.
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.
Giesel FL, Kratochwil C, Lindner T, Marschalek MM, Loktev A, Lehnert W, 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(3):386–92. https://doi.org/10.2967/jnumed.118.215913.
Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, et al. 68Ga-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.
Luo Y, Pan Q, Zhang W. IgG4-related disease revealed by (68)Ga-FAPI and (18)F-FDG PET/CT. Eur J Nucl Med Mol Imaging. 2019;46(12):2625–6. https://doi.org/10.1007/s00259-019-04478-2.
Pan Q, Luo Y, Zhang W. Recurrent immunoglobulin G4-related disease shown on 18F-FDG and 68Ga-FAPI PET/CT. Clin Nucl Med. 2020. https://doi.org/10.1097/RLU.0000000000002919.
Spadafora M, Pace L, Evangelista L, Mansi L, Del Prete F, Saladini G, et al. Risk-related (18)F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial. Eur J Nucl Med Mol Imaging. 2018;45(11):1908–14. https://doi.org/10.1007/s00259-018-4043-y.
Redondo-Cerezo E, Martinez-Cara JG, Jimenez-Rosales R, Valverde-Lopez F, Caballero-Mateos A, Jervez-Puente P, et al. Endoscopic ultrasound in gastric cancer staging before and after neoadjuvant chemotherapy. A comparison with PET-CT in a clinical series. United European Gastroenterol J. 2017;5(5):641–7. https://doi.org/10.1177/2050640616684697.
Jiang C, Chen Y, Zhu Y, Xu Y. Systematic review and meta-analysis of the accuracy of 18F-FDG PET/CT for detection of regional lymph node metastasis in esophageal squamous cell carcinoma. J Thoracic Dis. 2018;10(11):6066–76.
Jadvar H. Is there use for FDG-PET in prostate cancer? Semin Nucl Med. 2016;46(6):502–6. https://doi.org/10.1053/j.semnuclmed.2016.07.004.
Findlay JM, Antonowicz S, Segaran A, El Kafsi J, Zhang A, Bradley KM, et al. Routinely staging gastric cancer with (18)F-FDG PET-CT detects additional metastases and predicts early recurrence and death after surgery. Eur Radiol. 2019;29(5):2490–8. https://doi.org/10.1007/s00330-018-5904-2.
Sivesgaard K, Larsen LP, Sorensen M, Kramer S, Schlander S, Amanavicius N, et al. Diagnostic accuracy of CE-CT, MRI and FDG PET/CT for detecting colorectal cancer liver metastases in patients considered eligible for hepatic resection and/or local ablation. Eur Radiol. 2018;28(11):4735–47. https://doi.org/10.1007/s00330-018-5469-0.
Coccolini F, Gheza F, Lotti M, Virzi S, Iusco D, Ghermandi C, et al. Peritoneal carcinomatosis. World J Gastroenterol. 2013;19(41):6979–94. https://doi.org/10.3748/wjg.v19.i41.6979.
Shimada H, Okazumi S, Koyama M, Murakami K. Japanese Gastric Cancer Association Task Force for Research Promotion: clinical utility of 18F-fluoro-2-deoxyglucose positron emission tomography in gastric cancer. A systematic review of the literature. Gastric Cancer. 2011;14(1):13–21. https://doi.org/10.1007/s10120-011-0017-5.
Rubini G, Altini C, Notaristefano A, Merenda N, Rubini D, Ianora AA, et al. Role of 18F-FDG PET/CT in diagnosing peritoneal carcinomatosis in the restaging of patient with ovarian cancer as compared to contrast enhanced CT and tumor marker Ca-125. Rev Esp Med Nucl Imagen Mol. 2014;33(1):22–7. https://doi.org/10.1016/j.remn.2013.06.008.
Lindner T, Loktev A, Giesel F, Kratochwil C, Altmann A, Haberkorn U. Targeting of activated fibroblasts for imaging and therapy. EJNMMI Radiopharm Chem. 2019;4(1):16. https://doi.org/10.1186/s41181-019-0069-0.
Rohrich M, Loktev A, Wefers AK, Altmann A, Paech D, Adeberg S, et al. IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein-specific PET/CT. Eur J Nucl Med Mol Imaging. 2019;46(12):2569–80. https://doi.org/10.1007/s00259-019-04444-y.
Glaudemans AW, Enting RH, Heesters MA, Dierckx RA, van Rheenen RW, Walenkamp AM, et al. Value of 11C-methionine PET in imaging brain tumours and metastases. Eur J Nucl Med Mol Imaging. 2013;40(4):615–35. https://doi.org/10.1007/s00259-012-2295-5.
Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, et al. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med. 2005;46(6):945–52.
Afshar-Oromieh A, Hetzheim H, Kubler W, Kratochwil C, Giesel FL, Hope TA, et al. Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. Eur J Nucl Med Mol Imaging. 2016;43(9):1611–20. https://doi.org/10.1007/s00259-016-3419-0.
Sandstrom M, Velikyan I, Garske-Roman U, Sorensen J, Eriksson B, Granberg D, et al. Comparative biodistribution and radiation dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in patients with neuroendocrine tumors. J Nucl Med. 2013;54(10):1755–9. https://doi.org/10.2967/jnumed.113.120600.
Meyer C, Dahlbom M, Lindner T, Vauclin S, Mona C, Slavik R, et al. Radiation dosimetry and biodistribution of (68)Ga-FAPI-46 PET imaging in cancer patients. J Nucl Med. 2019. https://doi.org/10.2967/jnumed.119.236786.
Availability of data and material
Not applicable.
Funding
This work was funded by National Natural Science Foundation of China (Grant number 81772893 and 81701736) and the key medical and health projects in Xiamen (Grant number 3502Z20191104).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval
All procedures involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any experiments with animals.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Oncology - General
Electronic supplementary material
ESM 1
(DOCX 3907 kb)
Rights and permissions
About this article
Cite this article
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 47, 1820–1832 (2020). https://doi.org/10.1007/s00259-020-04769-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-020-04769-z