Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients

Frederik L Giesel, Clemens Kratochwil, Joel Schlittenhardt, Katharina Dendl, Matthias Eiber, Fabian Staudinger, Lukas Kessler, Wolfgang P Fendler, Thomas Lindner, Stefan A Koerber, Jens Cardinale, David Sennung, Manuel Roehrich, Juergen Debus, Mike Sathekge, Uwe Haberkorn, Jeremie Calais, Sebastian Serfling, Andreas L Buck, Frederik L Giesel, Clemens Kratochwil, Joel Schlittenhardt, Katharina Dendl, Matthias Eiber, Fabian Staudinger, Lukas Kessler, Wolfgang P Fendler, Thomas Lindner, Stefan A Koerber, Jens Cardinale, David Sennung, Manuel Roehrich, Juergen Debus, Mike Sathekge, Uwe Haberkorn, Jeremie Calais, Sebastian Serfling, Andreas L Buck

Abstract

Purpose: FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.

Material and methods: This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ).

Results: A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases.

Conclusion: Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

Keywords: Cancer-associated fibroblast; FAPI PET/CT; FDG PET/CT; Various cancer diseases.

Conflict of interest statement

UH, TL, CK, and FLG have a patent application for quinolone based FAP-targeting agents for imaging and therapy in nuclear medicine. UH, TL, CK, and FLG also have shares of a consultancy group for iTheranostics. FLG is also advisor at ABX, Telix, and SOFIE Biosciences. JCa is supported by the Prostate Cancer Foundation (2020 Young Investigator Award 20YOUN05) and the Society of Nuclear Medicine and Molecular imaging (2019 ERF Molecular Imaging Research Grant for Junior Academic Faculty). The other authors declare no conflict of interest regarding this manuscript.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Biodistribution (SUVmax and SUVmean) of 68Ga-FAPI in comparison to 18F-FDG in normal organs and tumor lesions (mean values and standard deviations; *: 68Ga-FAPI sign, higher; **: 18F-FDG sign, higher)
Fig. 2
Fig. 2
Intra-individual comparison of 18F-FDG and 68Ga-FAPI in a patient with oral squamous cell carcinoma presenting with inflammation in the colon as incidental finding in the 18F-FDG PET/CT (b), while no acute inflammatory process is associated with a 68Ga-FAPI-positive PET signal (a). The direct quantitative comparison presents a high SUVmax of 8.11 in the 18F-FDG PET/CT, while 68Ga-FAPI PET/CT demonstrates low tracer accumulation (SUVmax: 0.38)
Fig. 3
Fig. 3
Intra-individual comparison of 18F-FDG and 68Ga-FAPI in two patients with ovarian cancer (a) and pancreas cancer (b), respectively. Both present with strong 68Ga-FAP uptake in the primary and metastatic lesions while only slight to moderate uptake on 18F-FDG PET/CT (arrow: green (68Ga-FAPI) and red (18F-FDG)
Fig. 4
Fig. 4
A 68-year-old patient with a histologically confirmed squamous cell carcinoma of the edge of the tongue for pre-radiotherapeutic staging using PET/CT. The quantified uptake in the primary tumor (green arrow) on 68Ga-FAPI was SUVmax 20.26 compared to the 18F-FDG uptake with an SUVmax 13.35. As a secondary finding, fibrotic, scarred changes of the lung indicative of pulmonary fibrosis were observed (black arrow)
Fig. 5
Fig. 5
A 40-year-old female patient with ovarian cancer underwent restaging due to a suspicious subdiaphragmatic hepatic lesion. Tracer uptake in the normal liver parenchyma was markedly different on the two tracers: 68Ga-FAPI SUVmax 0.79 vs. 18F-FDG SUVmax 2.69. In the liver segment III and VII, a strong 68Ga-FAP uptake was found (green arrow) compared to 18F-FDG. The liver metastatic lesion in segment VII was not detected by 18F-FDG (red arrow)
Fig. 6
Fig. 6
A 55-year-old male underwent pre-operative staging after being diagnosed with colon cancer in the right ascending colon (green arrow). Both tracers presented uptake in the primary tumor (SUVmax: 68Ga-FAPI 6.25 vs. 18F-FDG 5.34), but there is considerably more background signal on 18F-FDG
Fig. 7
Fig. 7
An 80-year-old male patient with lung cancer (green arrows) was diagnosed by 18F-FDG PET/CT. 68Ga-FAPI PET/CT demonstrated similar tracer uptake (SUVmax: 18F-FDG 15.99 vs. 68Ga-FAPI 17.95). One advantage of 68Ga-FAPI in this instance is the lack of cardiac muscle uptake which is prominent with 18F-FDG (red arrow)

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