Comparative diagnostic performance of [68Ga]Ga-FAPI-46 and [18F]FDG PET/CT imaging for the detection of active lesions and disease stage evaluation in breast cancer patients

Document Type : Original Article

Authors

1 Department of Nuclear Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Research Center for Nuclear Medicine, Shraiati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s):  To compare the diagnostic performance of [68Ga]-Ga-FAPI-46 and [18F]-FDG PET/CT imaging for the detection of lesions and disease staging in breast cancer.
Methods: Twelve female patients with breast cancer (mean age= 49.2±13.29 years) and previous [18F]-FDG PET/CT were recruited in the study. [68Ga]Ga-FAPI-46 imaging performed in all patients within one month after [18F]-FDG PET/CT imaging. The acquired PET/CT data with both tracers were reconstructed. Tracer avid lesions with each PET tracer were identified and the semi-quantitative parameters i.e. SUVmax, lesion counts and target-to-background ratio (TBRmax) were analyzed.
Results: Physiologic distribution of [68Ga]-Ga-FAPI-46 was observed in the liver, blood pool and kidneys, whereas no tracer uptake was noted in the brain and heart. The mean liver SUVmax for [68Ga] Ga-FAPI-46 was 1.5±0.1 which was lower than that noted for [18F]-FDG PET/CT (2.9±0.2). Likewise, the mean blood pool SUVmax value for [68Ga]-Ga-FAPI-46 was lower than [18F]-FDG PET/CT (1.7±0.1 versus 2.0±0.1). [68Ga]-Ga-FAPI-46 PET/CT demonstrated higher tracer uptake in the lesions detected in the brain, bone, internal mammary and lymph nodes in 4/12 patients. The overall lesions detections and the mean SUVmax values did not differ significantly between the two techniques. On the other hand, [68Ga]-Ga-FAPI-46 demonstrated higher mean TBRmax than [18F] FDG PET/CT particularly for lesions detected in kidneys, chest wall, mediastinum, and musculoskeletal lesions. However, both techniques offered identical TNM staging.
Conclusion: The findings of this preliminary study demonstrated that [68Ga]-Ga-FAPI-46 and [18F]-FDG PET/CT offered identical disease staging in the breast cancer patients. [68Ga]-Ga-FAPI-46 showed lower liver and blood pool uptake and an enhanced tumor-to-background ratio, thereby suggesting its potential for improved lesions detection. This may open opportunity for emerging FAP based radioligand for therapeutic applications in advanced stage breast cancers. However, this needs validation in a larger number of patients.

Keywords

Main Subjects


  1. Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. The Breast. 2022; 66: 15-23.
  2. Rong J, Wang S, Ding Q, Yun M, Zheng Z, Ye S. Comparison of 18FDG PET-CT and bone scintigraphy for detection of bone metastases in breast cancer patients. A meta-analysis. Surgical Oncology. 2013; 22(2): 86-91.
  3. Kitajima K, Miyoshi Y. Present and future role of FDG-PET/CT imaging in the management of breast cancer. Japanese Journal of Radiology. 2016; 34(3): 167-80.
  4. Bertagna F, Treglia G, Orlando E, Dognini L, Giovanella L, Sadeghi R, et al. Prevalence and clinical significance of incidental F18-FDG breast uptake: a systematic review and meta-analysis. Japanese Journal of Radiology. 2014; 32(2): 59-68.
  5. Ulaner GA. PET/CT for patients with breast cancer: where is the clinical impact? American Journal of Roentgenology. 2019; 213(2): 254-65.
  6. Hadebe B, Harry L, Ebrahim T, Pillay V, Vorster M. The role of PET/CT in breast cancer. Diagnostics. 2023; 13(4): 597.
  7. Kalluri R. The biology and function of fibroblasts in cancer. Nature Reviews Cancer. 2016; 16(9): 582-98.
  8. Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes & development. 2016; 30(9): 1002-19.
  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 – Clinical Applications. 2014; 8(5-6): 454-63.
  10. 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. Journal of Nuclear Medicine. 2019; 60(6): 801-5.
  11. Kömek H, Can C, Güzel Y, Oruç Z, Gündoğan C, Yildirim ÖA, et al. 68Ga-FAPI-04 PET/CT, a new step in breast cancer imaging: a comparative pilot study with the 18F-FDG PET/CT. Annals of nuclear medicine. 2021; 35: 744-52.
  12. Elboga U, Sahin E, Kus T, Cayirli YB, Aktas G, Uzun E, et al. Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer. Annals of Nuclear Medicine. 2021; 35(12): 1321-31.
  13. Backhaus P, Burg MC, Roll W, Büther F, Breyholz H-J, Weigel S, et al. Simultaneous FAPI PET/MRI targeting the fibroblast-activation protein for breast cancer. Radiology. 2022; 302(1): 39-47.
  14. Eshet Y, Tau N, Apter S, Nissan N, Levanon K, Bernstein-Molho R, et al. The role of 68Ga-FAPI PET/CT in detection of metastatic lobular breast cancer. Clinical Nuclear Medicine. 2022; 10: 1097.
  15. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2018; 68(6): 394-424.
  16. Marino MA, Helbich T, Baltzer P, Pinker-Domenig K. Multiparametric MRI of the breast: A review. Journal of Magnetic Resonance Imaging. 2018; 47(2): 301-15.
  17. Tadesse GF, Geramifar P, Ghafarian P, Cheka EE, Tegaw EM, Feyisa SG, et al. Molecular imaging approaches in the diagnosis of breast cancer: A systematic review and meta-analysis. Iranian Journal of Nuclear Medicine. 2020; 28(1): 1-13.
  18. Kumar R, Chauhan A, Zhuang H, Chandra P, Schnall M, Alavi A. Clinicopathologic factors associated with false negative FDG–PET in primary breast cancer. Breast Cancer Research and Treatment. 2006; 98(3): 267-74.
  19. Avril N, Rose C, Schelling M, Dose J, Kuhn W, Bense S, et al. Breast imaging with positron emission tomography and fluorine-18 fluorodeoxyglucose: use and limitations. Journal of clinical oncology. 2000; 18(20): 3495-502.
  20. Hirose Y, Kaida H, Ishibashi M, Kawahara A, Kobayashi M, Hayabuchi N. Glucose transporter expression of intraductal papilloma of the breast detected by fluoro-deoxyglucose positron emission tomo-graphy. Japanese Journal of Radiology. 2011; 29(3): 217-21.
  21. Novruzov F, Mehdi E, Orucova N, Aliyeva G, Shukurov R, Dadashov Z, et al. Head to head comparison of 68Ga-FAPI-46 PET/CT and 18-FDG PET/CT in breast carcinoma staging: a clinical trial update from Azerbaijan. Journal of Nuclear Medicine. 2022; 63(supplement 2): 2372.
  22. Evangelista L, Filippi L, Schillaci O. What radiolabeled FAPI pet can add in breast cancer? A systematic review from Ann Nucl Med. 2023; 37(8): 442-50.
  23. Wegen S, van Heek L, Linde P, Claus K, Akuamoa-Boateng D, Baues C, et al. Head-to-head comparison of [68 Ga] Ga-FAPI-46-PET/CT and [18F] F-FDG-PET/CT for radiotherapy planning in head and neck cancer. Molecular imaging and biology. 2022; 24(6): 986-94.
  24. Wegen S, Roth KS, Weindler J, Claus K, Linde P, Trommer M, et al. First clinical experience with [68Ga]Ga-FAPI-46-PET/CT versus [18F]F-FDG PET/CT for nodal staging in cervical cancer. Clin Nucl Med. 2023; 48(2): 150-5.
  25. Li L, Hu X, Ma J, Yang S, Gong W, Zhang C. A systematic review of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT in the diagnostic value of malignant tumor bone metastasis. Frontiers in Oncology. 2022; 12:978506.
  26. Hadad B, Aryana K, Kamali H, Askari E. 99m Tc-HYNIC-FAPI-46 SPECT/CT Uptake in Lactating Breasts. Clin Nucl Med. 2024; 49(4): e184-e5.
  27. Lin R, Lin Z, Zhang J, Yao S, Miao W. Increased 68Ga-FAPI-04 uptake in Schmorl node in a patient with gastric cancer. Clinical Nuclear Medicine. 2021; 46(8): 700-2.
  28. Can C, Gündoğan C, Güzel Y, Kaplan İ, Kömek H. 68Ga-FAPI uptake of thyroiditis in a patient with breast cancer. Clinical Nuclear Medicine. 2021; 46(8): 683-5.
  29. Liu H, Wang Y, Zhang W, Cai L, Chen Y. Elevated 68Ga-FAPI activity in splenic hemangioma and pneumonia. Clinical Nuclear Medicine. 2021; 46(8): 694-6.
  30. Zhang Y, Cai J, Wu Z, Yao S, Miao W. Intense [68Ga] Ga-FAPI-04 uptake in solitary fibrous tumor/hemangiopericytoma of the central nervous system. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48: 4103-4.
  31. Liu H, Chen Z, Yang X, Fu W, Chen Y. Increased 68Ga-FAPI uptake in chronic cholecystitis and degenerative osteophyte. Clinical Nuclear Medicine. 2021; 46(7): 601-2.
  32. Zhang X, Song W, Qin C, Liu F, Lan X. Non-malignant findings of focal 68Ga-FAPI-04 uptake in pancreas. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(8): 2635-41.
  33. Röhrich M, Naumann P, Giesel FL, Choyke PL, Staudinger F, Wefers A, et al. Impact of 68Ga-FAPI PET/CT imaging on the therapeutic management of primary and recurrent pancreatic ductal adenocarcinomas. Journal of Nuclear Medicine. 2021; 62(6): 779-86.
  34. Kosmala A, Serfling SE, Schlötelburg W, Lindner T, Michalski K, Schirbel A, et al. Impact of 68Ga-FAPI-04 PET/CT on staging and therapeutic management in patients with digestive system tumors. Clin Nucl Med. 2023; 48(1): 35-42.