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

Barbara Kreppel; Maria Angeles Gonzalez-Carmona; Georg Feldmann; Jim Küppers; Euy Sung Moon; Milka Marinova; Ralph Alexander Bundschuh; Glen Kristiansen; Markus Essler; Frank Roesch; Florian Christoph Gaertner

doi:10.1055/a-1521-8604

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

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

¹Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Maria Angeles Gonzalez-Carmona

²Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Georg Feldmann

³Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Jim Küppers

¹Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Euy Sung Moon

⁴Department of Chemistry, Johannes Gutenberg University, Mainz, Germany (Ringgold ID: RIN9182)

,

Milka Marinova

⁵Department of Radiology, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Ralph Alexander Bundschuh

¹Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Glen Kristiansen

⁶Institute of Pathology, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Markus Essler

⁷Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Bonn, Bonn, Germany (Ringgold ID: RIN39062)

,

Frank Roesch

⁴Department of Chemistry, Johannes Gutenberg University, Mainz, Germany (Ringgold ID: RIN9182)

,

Florian Christoph Gaertner

¹Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany (Ringgold ID: RIN39062)

› Institutsangaben

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 FDG_SUVmax correlated positively (rho = 0.543, p < 0.05) and DOTATOC_SUVmax 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 FAPi_SUVmax and Ki-67 (rho = 0.382, p > 0.05). FAPi_TF correlated positively (rho = 0.770, p < 0.01) and DOTATOC_TF correlated negatively (rho = –0.828, p < 0.01) with Ki-67, both significantly with high correlation coefficients. FDG_TF also correlated significantly with Ki-67, with a moderate correlation coefficient (rho = 0.524, p < 0.05). The ratio FAPi_VOL:DOTATOC_VOL showed a significant and strong correlation with Ki-67 (rho = 0.808, p < 0.01).

Conclusion The ratio FAPi_VOL:DOTATOC_VOL 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, SUV_max und PET-positiver Tumorfraktion (TF) delineiert. Die PET-Parameter wurden mit Ki-67 korreliert.

Ergebnisse FDG_SUVmax zeigte eine positive (rho=0,543; p<0,05) und DOTATOC_SUVmax eine negative (rho=–0,618; p<0,05) Korrelation mit Ki-67, die Korrelationskoeffizienten lagen im moderaten Bereich. Es gab keine signifikante Korrelation zwischen FAPi_SUVmax und Ki-67 (rho=0,382; p>0,05). FAPi_TF korrelierte positiv (rho=0,770; p<0,01) und DOTATOC_TF korrelierte negativ (rho=–0,828; p<0,01) mit Ki-67, beide jeweils signifikant mit hohen Korrelationskoeffizienten. FDG_TF korrelierte ebenfalls signifikant mit Ki-67, mit einem moderaten Korrelationskoeffizienten (rho=0,524; p<0,05). Die Ratio FAPi_VOL:DOTATOC_VOL zeigte eine signifikante und starke Korrelation mit Ki-67 (rho=0,808; p<0,01).

Schlussfolgerung Die Ratio FAPi_VOL:DOTATOC_VOL 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

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Referenzen

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