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Ga-FAPI-46 PET/CT for cancer imaging: Results of a single-center, prospective, interventional, single-arm clinical trial.
Authors: Pabst Kim M. , Bartel Timo , Sandach Patrick , Laschinsky Christina , Weber Manuel M. , Kessler Lukas , Küper Alina T. , Hadaschik Boris A. , Kesch Claudia , Hamacher Rainer , Kasper Stefan , Podleska Lars E. , Siveke Jens T. , Eckstein Markus , von Tresckow Bastian , Kuemmel Sherko , Reinacher-Schick Anke , Uhl Waldemar , Herrmann Ken , Fendler Wofgang P. 
Published: February 2025

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Background:
Fibroblast activation protein (FAP) is highly expressed on tumor-associated fibroblasts. FAP-directed radioligand positron emission tomography (
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Ga-FAPI-46 PET) is a novel tool for cancer imaging. However, its diagnostic performance, especially in genitourinary (GU) cancers, is still unclear. Here, we aim to compare diagnostic performance of
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Ga-FAPI-46 and
18
F-FDG PET, validated by histopathology.
Methods:
Patients (pts) at initial staging/restaging with (a) proven or suspected malignancy, (b) any tumor diameter > 1 cm, (c) planned or performed biopsy/surgery within 8 weeks prior to or after
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Ga-FAPI-46 PET, and (d) no prior external beam radiation or systemic tumor therapy within 1 month underwent
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Ga-FAPI-46 and clinical
18
F-FDG PET on subsequent days. For comparison, patient-based and region-based (local, nodal, distant organ or soft tissue, bone) image analysis was performed by three blinded nuclear medicine physicians, separate for each PET modality. Positive predictive value (PPV) and sensitivity (SE) were evaluated based on histopathologic results, and compared in the subgroups of GU cancers, sarcoma, and others. Inter-reader reproducibility was assessed using Fleiss‘ kappa.
Results:
A total of n=158 pts (median age: 62 years, male/female: n=101 (63.9%)/57 (36.1%)) were enrolled. 155 (98.1%)/152 (96.2%) pts underwent
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Ga-FAPI-46/
18
F-FDG PET/CT. Histopathologic validation was available in n=145 (91.8%) pts. N=54 (34.2%)/28 (17.7%)/76 (48.1%) pts were diagnosed with GU cancers/sarcoma/others. Patient-based PPV/SE for
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Ga-FAPI-46 (
18
F-FDG) PET were 94/72% (97/71%) for GU cancers, 100/96% (100/96%) for sarcoma, and 100/91% (100/88%) for others. Region-based PPV/SE for
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Ga-FAPI-46 (
18
F-FDG) PET were 93/71% (97/70%) for GU cancers, 100/94% (97/90%) for sarcoma, and 99/90% (93/85%) for others. Patient-based inter-reader reproducibility for
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Ga-FAPI-46 (
18
F-FDG) PET was 0.71 (0.43) for GU cancers, 1.0 (0.21) for sarcoma, and 0.6 (0.53) for others.
Conclusions:
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Ga-FAPI-46 and
18
F-FDG PET demonstrate similar accuracy for tumor detection and localization of GU cancers. However, inter-reader reproducibility was superior for
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Ga-FAPI-46 (substantial agreement) compared to
18
F-FDG PET (moderate agreement). Clinical trial information:
NCT05160051
.

Patient characteristics.

All patients n=158
All regions n=186

Diagnosis
n (pts)
% (pts)
n (regions)
% (regions)

Genitourinary CancersRenal cell carcinomaUrothelial carcinomaProstate cancerSeminomaOthers

54
3314322

34.2
20.98.91.91.31.3

63
3816414

33.9
20.48.62.20.52.2

Sarcoma

28

17.7

32

17.2

Others*

76

48.1

91

48.9

*Including breast cancer, cholangiocarcinoma, colorectal cancer, endometrial cancer, esophageal cancer, head and neck cancer, lymphoma, multiple myeloma, neuroendocrine, NSCLC, pancreatic cancer, thyroid cancer, unknown primary, others.