Diagnostic Potential of Supplemental Static and Dynamic 68Ga-FAPI-46 PET for Primary 18F-FDG-Negative Pulmonary Lesions

Manuel Röhrich; Johanna Daum; Ewgenija Gutjahr; Anna-Maria Spektor; Frederik M Glatting; Yasemin Aylin Sahin; Hans Georg Buchholz; Jorge Hoppner; Cathrin Schroeter; Eleni Mavriopoulou; Kai Schlamp; Matthias Grott; Florian Eichhorn; Claus Peter Heußel; Hans Ulrich Kauczor; Michael Kreuter; Frederik Giesel; Mathias Schreckenberger; Hauke Winter; Uwe Haberkorn

doi:10.2967/jnumed.123.267103

Diagnostic Potential of Supplemental Static and Dynamic ⁶⁸Ga-FAPI-46 PET for Primary ¹⁸F-FDG-Negative Pulmonary Lesions

J Nucl Med. 2024 Apr 11:jnumed.123.267103. doi: 10.2967/jnumed.123.267103. Online ahead of print.

Authors

Manuel Röhrich^{1

2

3}, Johanna Daum^{4

3}, Ewgenija Gutjahr⁵, Anna-Maria Spektor^{4

3}, Frederik M Glatting^{4

6

7}, Yasemin Aylin Sahin², Hans Georg Buchholz², Jorge Hoppner^{4

3}, Cathrin Schroeter^{4

3}, Eleni Mavriopoulou^{4

3}, Kai Schlamp^{3

8}, Matthias Grott^{3

9}, Florian Eichhorn^{3

9}, Claus Peter Heußel^{3

8}, Hans Ulrich Kauczor^{3

10

11}, Michael Kreuter^{12

13}, Frederik Giesel^{4

3

14

15

16}, Mathias Schreckenberger², Hauke Winter^{3

8}, Uwe Haberkorn^{4

3

10

17}

Affiliations

¹ Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany; manuel.roehrich@med.uni-heidelberg.de.
² Department of Nuclear Medicine, University Hospital Mainz, Mainz, Germany.
³ German Center of Lung Research, Heidelberg, Germany.
⁴ Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
⁵ Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
⁶ Clinical Cooperation Unit Molecular and Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
⁷ Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany.
⁸ Department of Radiology, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany.
⁹ Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg, Heidelberg, Germany.
¹⁰ Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany.
¹¹ Center for Interstitial and Rare Lung Diseases, Pneumology, and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
¹² Department of Pneumology, Mainz Center for Pulmonary Medicine, Mainz University, Mainz, Germany.
¹³ Medical Center and Department of Pulmonary, Critical Care, and Sleep Medicine, Marienhaus Clinic Mainz, Mainz, Germany.
¹⁴ Department of Nuclear Medicine, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
¹⁵ Institute for Radiation Sciences, Osaka University, Osaka, Japan.
¹⁶ German Cancer Consortium, Heidelberg, Germany; and.
¹⁷ Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany.

PMID: 38604763
DOI: 10.2967/jnumed.123.267103

Abstract

PET using ⁶⁸Ga-labeled fibroblast activation protein (FAP) inhibitors (FAPIs) holds high potential for diagnostic imaging of various malignancies, including lung cancer (LC). However, ¹⁸F-FDG PET is still the clinical gold standard for LC imaging. Several subtypes of LC, especially lepidic LC, are frequently ¹⁸F-FDG PET-negative, which markedly hampers the assessment of single pulmonary lesions suggestive of LC. Here, we evaluated the diagnostic potential of static and dynamic ⁶⁸Ga-FAPI-46 PET in the ¹⁸F-FDG-negative pulmonary lesions of 19 patients who underwent surgery or biopsy for histologic diagnosis after PET imaging. For target validation, FAP expression in lepidic LC was confirmed by FAP immunohistochemistry. Methods: Hematoxylin and eosin staining and FAP immunohistochemistry of 24 tissue sections of lepidic LC from the local tissue bank were performed and analyzed visually. Clinically, 19 patients underwent static and dynamic ⁶⁸Ga-FAPI-46 PET in addition to ¹⁸F-FDG PET based on individual clinical indications. Static PET data of both examinations were analyzed by determining SUV_max, SUV_mean, and tumor-to-background ratio (TBR) against the blood pool, as well as relative parameters (⁶⁸Ga-FAPI-46 in relation to¹⁸F-FDG), of histologically confirmed LC and benign lesions. Time-activity curves and dynamic parameters (time to peak, slope, k ₁, k ₂, k ₃, and k ₄) were extracted from dynamic ⁶⁸Ga-FAPI-46 PET data. The sensitivity and specificity of all parameters were analyzed by calculating receiver-operating-characteristic curves. Results: FAP immunohistochemistry confirmed the presence of strongly FAP-positive cancer-associated fibroblasts in lepidic LC. LC showed markedly elevated ⁶⁸Ga-FAPI-46 uptake, higher TBRs, and higher ⁶⁸Ga-FAPI-46-to-¹⁸F-FDG ratios for all parameters than did benign pulmonary lesions. Dynamic imaging analysis revealed differential time-activity curves for LC and benign pulmonary lesions: initially increasing time-activity curves with a decent slope were typical of LC, and steadily decreasing time-activity curve indicated benign pulmonary lesions, as was reflected by a significantly increased time to peak and significantly smaller absolute values of the slope for LC. Relative ⁶⁸Ga-FAPI-46-to-¹⁸F-FDG ratios regarding SUV_max and TBR showed the highest sensitivity and specificity for the discrimination of LC from benign pulmonary lesions. Conclusion: ⁶⁸Ga-FAPI-46 PET is a powerful new tool for the assessment of single ¹⁸F-FDG-negative pulmonary lesions and may optimize patient stratification in this clinical setting.

Keywords: FAPI; PET; fibroblast activation protein; lung cancer; pulmonary lesions.