PDF herunterladen
Nuklearmedizin 2021; 60(05): 344-354
DOI: 10.1055/a-1521-8604
Original Article

Fibroblast activation protein inhibitor (FAPi) positive tumour fraction on PET/CT correlates with Ki-67 in liver metastases of neuroendocrine tumours

Detektion Fibroblast Activation Protein Inhibitor (FAPi)-positiver Tumoranteile in der PET/CT bei Lebermetastasen neuroendokriner Tumore: Korrelation mit dem Proliferationsindex Ki-67
Barbara Kreppel
1   Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Maria Angeles Gonzalez-Carmona
2   Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Georg Feldmann
3   Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Jim Küppers
1   Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Euy Sung Moon
4   Department of Chemistry, Johannes Gutenberg University, Mainz, Germany (Ringgold ID: RIN9182)
,
Milka Marinova
5   Department of Radiology, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Ralph Alexander Bundschuh
1   Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Glen Kristiansen
6   Institute of Pathology, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Markus Essler
7   Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Bonn, Bonn, Germany (Ringgold ID: RIN39062)
,
Frank Roesch
4   Department of Chemistry, Johannes Gutenberg University, Mainz, Germany (Ringgold ID: RIN9182)
,
Florian Christoph Gaertner
1   Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Aim Gallium-68-labelled inhibitors of the fibroblast activation protein (FAPi) enable positron emission tomography/computed tomography (PET/CT) imaging of fibroblast activation. We evaluated if [68Ga]Ga-DATA5m.SA.FAPi PET/CT is related to Ki-67 as a marker of tumour aggressiveness in patients with liver metastases of NET.

Methods Thirteen patients with liver metastases of a histologically confirmed NET who underwent PET/CT with [68Ga]Ga-DATA5m.SA.FAPi, [18F]FDG and [68Ga]Ga-DOTA-TOC were retrospectively analyzed. PET-positive liver tumour volumes were segmented for calculation of volume, SUVmax and PET-positive tumour fraction (TF). PET parameters were correlated with Ki-67.

Results FDGSUVmax correlated positively (rho = 0.543, p < 0.05) and DOTATOCSUVmax correlated negatively (rho = –0.618, p < 0.05) with Ki-67, the correlation coefficients were in the moderate range. There was no significant correlation between FAPiSUVmax and Ki-67 (rho = 0.382, p > 0.05). FAPiTF correlated positively (rho = 0.770, p < 0.01) and DOTATOCTF correlated negatively (rho = –0.828, p < 0.01) with Ki-67, both significantly with high correlation coefficients. FDGTF also correlated significantly with Ki-67, with a moderate correlation coefficient (rho = 0.524, p < 0.05). The ratio FAPiVOL:DOTATOCVOL showed a significant and strong correlation with Ki-67 (rho = 0.808, p < 0.01).

Conclusion The ratio FAPiVOL:DOTATOCVOL might serve as a clinical parameter for the assessment of dedifferentiation and aggressiveness of liver metastases in patients with NET. [68Ga]Ga-DATA5m.SA.FAPi might hold potential for identification of high-risk patients. Further studies are warranted to evaluate its prognostic significance in comparison to [18F]FDG in patients with NET.

Zusammenfassung

Ziel Gallium-68-markierte Inhibitoren des Fibroblasten-Aktivierungsproteins (FAPi) ermöglichen die Bildgebung der Fibroblastenaktivierung in der Positronen-Emissions-Tomografie/Computertomografie (PET/CT). Wir untersuchten den Zusammenhang zwischen [68Ga]Ga-DATA5m.SA.FAPi PET/CT und Ki-67 als Marker für Tumoraggressivität bei Patienten mit Lebermetastasen eines NET.

Methoden Dreizehn Patienten mit Lebermetastasen eines histologisch bestätigten NET, die sich einer PET/CT mit [68Ga]Ga-DATA5m.SA.FAPi, [18F]FDG und [68Ga]Ga-DOTA-TOC unterzogen, wurden retrospektiv analysiert. PET-positive Lebertumorvolumina wurden für die Berechnung von Volumen, SUVmax und PET-positiver Tumorfraktion (TF) delineiert. Die PET-Parameter wurden mit Ki-67 korreliert.

Ergebnisse FDGSUVmax zeigte eine positive (rho=0,543; p<0,05) und DOTATOCSUVmax eine negative (rho=–0,618; p<0,05) Korrelation mit Ki-67, die Korrelationskoeffizienten lagen im moderaten Bereich. Es gab keine signifikante Korrelation zwischen FAPiSUVmax und Ki-67 (rho=0,382; p>0,05). FAPiTF korrelierte positiv (rho=0,770; p<0,01) und DOTATOCTF korrelierte negativ (rho=–0,828; p<0,01) mit Ki-67, beide jeweils signifikant mit hohen Korrelationskoeffizienten. FDGTF korrelierte ebenfalls signifikant mit Ki-67, mit einem moderaten Korrelationskoeffizienten (rho=0,524; p<0,05). Die Ratio FAPiVOL:DOTATOCVOL zeigte eine signifikante und starke Korrelation mit Ki-67 (rho=0,808; p<0,01).

Schlussfolgerung Die Ratio FAPiVOL:DOTATOCVOL könnte als klinischer Parameter zur Beurteilung der Entdifferenzierung und Aggressivität von Lebermetastasen bei Patienten mit NET dienen. [68Ga]Ga-DATA5m.SA.FAPi könnte Potenzial für die Identifizierung von Hochrisikopatienten haben. Weitere Studien sind gerechtfertigt, um die prognostische Signifikanz im Vergleich zu [18F]FDG bei Patienten mit NET zu bewerten.

Schlüsselwörter

Fibroblasten-Aktivierungsprotein-Inhibitor (FAPi) - Gallium-68 PET/CT - neuroendokrine Tumore (NET) - Proliferationsindex - Ki-67 - Grading

Keywords

fibroblast activation protein inhibitor (FAPi) - Gallium-68 PET/CT - neuroendocrine tumours (NET) - proliferation index - Ki-67 - grading

Supporting information



Publikationsverlauf

Eingereicht: 16. April 2021

Angenommen nach Revision: 31. Mai 2021

Artikel online veröffentlicht:
13. Juli 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Pavel M, Öberg K, Falconi M. et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31: 844-860
    CrossrefPubMedSuche in Google Scholar
  • 2 Carideo L, Prosperi D, Panzuto F. et al. Role of combined [68Ga]Ga-DOTA-SST analogues and [18F]FDG PET/CT in the management of GEP-NENs: A systematic review. J Clin Med 2019; 8: 1032
    CrossrefPubMedSuche in Google Scholar
  • 3 Barrio M, Czernin J, Fanti S. et al. The impact of somatostatin receptor-directed PET/CT on the management of patients with neuroendocrine tumor: A systematic review and meta-analysis. J Nucl Med 2017; 58: 756-761
    CrossrefPubMedSuche in Google Scholar
  • 4 Laskaratos FM, Rombouts K, Caplin M. et al. Neuroendocrine tumors and fibrosis: An unsolved mystery?. Cancer 2017; 123: 4770-4790
    CrossrefPubMedSuche in Google Scholar
  • 5 Loktev A, Lindner T, Mier W. et al. A tumor-imaging method targeting cancer-associated fibroblasts. J Nucl Med 2018; 59: 1423-1429
    CrossrefPubMedSuche in Google Scholar
  • 6 Wikberg ML, Edin S, Lundberg IV. et al. High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumor Biol 2013; 34: 1013-1020
    CrossrefPubMedSuche in Google Scholar
  • 7 Henry LR, Lee HO, Lee JS. et al. Clinical implications of fibroblast activation protein in patients with colon cancer. Clin Cancer Res 2007; 13: 1736-1741
    CrossrefPubMedSuche in Google Scholar
  • 8 Saigusa S, Toiyama Y, Tanaka K. et al. Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy. Int J Oncol 2011; 38: 655-663
    CrossrefPubMedSuche in Google Scholar
  • 9 Li M, Cheng X, Rong R. et al. High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer. BMC Cancer 2020; 20: 1032
    CrossrefPubMedSuche in Google Scholar
  • 10 Coto-Llerena M, Ercan C, Kancherla V. et al. High expression of FAP in colorectal cancer is associated with angiogenesis and immunoregulation processes. Front Oncol 2020; 10: 979
    CrossrefPubMedSuche in Google Scholar
  • 11 Solano-Iturri JD, Beitia M, Errarte P. et al. Altered expression of fibroblast activation protein-α (FAP) in colorectal adenoma-carcinoma sequence and in lymph node and liver metastases. Aging (Albany NY) 2020; 12: 10337-10358
    CrossrefPubMedSuche in Google Scholar
  • 12 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: 801-805
    CrossrefPubMedSuche in Google Scholar
  • 13 Kreppel B, Gärtner FC, Marinova M. et al. 68Ga. Nuklearmedizin 2020; 59: 387-389
    Thieme ConnectPubMedSuche in Google Scholar
  • 14 Gaertner FC, Plum T, Kreppel B. et al. Clinical evaluation of [68Ga]Ga-DATA-TOC in comparison to [68Ga]Ga-DOTA-TOC in patients with neuroendocrine tumours. Nucl Med Biol 2019; 76–77: 1-9
    CrossrefPubMedSuche in Google Scholar
  • 15 Singh S, Hallet J, Rowsell C. et al. Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease. Eur J Surg Oncol 2014; 40: 1517-1522
    CrossrefPubMedSuche in Google Scholar
  • 16 Shi H, Zhang Q, Han C. et al. Variability of the Ki-67 proliferation index in gastroenteropancreatic neuroendocrine neoplasms – a single-center retrospective study. BMC Endocr Disord 2018; 18: 51
    CrossrefPubMedSuche in Google Scholar
  • 17 Ezziddin S, Adler L, Sabet A. et al. Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine neoplasms by 18F-FDG PET: Feasibility of a metabolic grading system. J Nucl Med 2014; 55: 1260-1266
    CrossrefPubMedSuche in Google Scholar
  • 18 Panagiotidis E, Alshammari A, Michopoulou S. et al. Comparison of the impact of 68Ga-DOTATATE and 18F-FDG PET/CT on clinical management in patients with neuroendocrine tumors. J Nucl Med 2017; 58: 91-96
    CrossrefPubMedSuche in Google Scholar
  • 19 Chan DLH, Pavlakis N, Schembri GP. et al. Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: Proposal for a novel grading scheme with prognostic significance. Theranostics 2017; 7: 1149-1158
    CrossrefPubMedSuche in Google Scholar
  • 20 Gress TM, Albert J, Alfke H. et al. Practice guideline neuroendocrine tumors: AWMF-Reg021–27. Z Gastroenterol 2018; 56: 583-681
    Thieme ConnectPubMedSuche in Google Scholar
  • 21 Zaknun JJ, Bodei L, Mueller-Brand J. et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013; 40: 800-816
    CrossrefPubMedSuche in Google Scholar
  • 22 Ezziddin S, Opitz M, Attassi M. et al. Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2011; 38: 459-466
    CrossrefPubMedSuche in Google Scholar
  • 23 Sorbye H, Welin S, Langer SW. et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): The NORDIC NEC study. Ann Oncol 2013; 24: 152-160
    CrossrefPubMedSuche in Google Scholar
  • 24 Rinke A, Gress TM. Neuroendocrine cancer, therapeutic strategies in G3 cancers. Digestion 2017; 95: 109-114
    CrossrefPubMedSuche in Google Scholar
  • 25 Altmann A, Haberkorn U, Siveke J. The Latest Developments in Imaging of Fibroblast Activation Protein. J Nucl Med 2021; 62: 160-167
    CrossrefPubMedSuche in Google Scholar
  • 26 Hicks RJ, Roselt PJ, Kallur KG. et al. FAPI PET/CT: Will It End the Hegemony of 18 F-FDG in Oncology?. J Nucl Med 2021; 62: 296-302
    CrossrefPubMedSuche in Google Scholar