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. 2022 Aug;24(4):651-658.
doi: 10.1007/s11307-022-01715-3. Epub 2022 Mar 29.

Head-to-head Intra-individual Comparison of [68Ga]-FAPI and [18F]-FDG PET/CT in Patients with Bladder Cancer

E Novruzov  1 , K Dendl  1   2 , H Ndlovu  3 , P L Choyke  4 , M Dabir  1 , M Beu  1 , F Novruzov  5 , E Mehdi  5 , F Guliyev  6 , S A Koerber  7 , I Lawal  4 , G Niegisch  8 , J Debus  7 , U Haberkorn  2 , M Sathekge  3 , F L Giesel  9   10
Affiliations

Head-to-head Intra-individual Comparison of [68Ga]-FAPI and [18F]-FDG PET/CT in Patients with Bladder Cancer

E Novruzov et al. Mol Imaging Biol. 2022 Aug.

Abstract

Aim/purpose: Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [18F]FDG PET/CT. 68Ga-labeled fibroblast activation protein inhibitor-([68Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [18F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [68Ga]FAPI in patients with bladder cancer.

Material and methods: This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [68Ga]FAPI and [18F]FDG PET/CT scans with a median time interval of 5 days (range 1-20 days). Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool.

Results: Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [68Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [68Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [18F]FDG PET/CT with higher mean SUVmax (8.2 vs. 4.6; p = 0.01). Furthermore, [68Ga]FAPI detected additional 30% (n = 9) lesions, missed by [18F]FDG. TBR demonstrated favorable uptake for [68Ga]FAPI in comparison to [18F]FDG. Significant differences were determined with regard to metastasis/blood pool ([68Ga]FAPI 5.3 vs [18F]FDG 1.9; p = 0.001).

Conclusion: [68Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [18F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies.

Keywords: Bladder cancer; FAPI; Fibroblast activation protein; PET; Urothelial carcinoma.

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Conflict of interest statement

UH and FLG have a patent application for quinolone based FAP-targeting agents for imaging and therapy in nuclear medicine. UH and FLG also have shares of a consultancy group for iTheranostics. FLG is also advisor at ABX, Telix, and SOFIE Biosciences. SAK reports grants from Viewray Inc. and honoraria from IBA Dosimetry, outside the submitted work. The other authors declare no conflict of interest regarding this manuscript.

Figures

Fig. 1
Fig. 1
Biodistribution (SUVmax and SUVmean) of [68 Ga]FAPI in comparison to [18F]FDG in normal organs and metastatic lesions (mean values and standard deviations)
Fig. 2
Fig. 2
A 60-year-old patient in the 7th year of follow-up for bladder cancer underwent restaging due to a suspicious lung finding on the right side. The PET/CT scan shows [68 Ga]FAPI avid hilar lymph node metastasis (red arrow) as well as both [68 Ga]FAPI and [18F]FDG avid pulmonary metastasis in the right lung. The quantified uptake in the hilar lymph nodes on [68 Ga]FAPI (d -f) was SUVmax 5,5 compared to the [18F]FDG uptake (a–c.) with an SUVmax 1,4 and in the lung metastasis (green arrow) on the right side on [68 Ga]FAPI was SUVmax 7,0 compared to the [18F]FDG uptake with an SUVmax 6,3 (green arrow = [18F]FDG, red arrow = [68Ga]FAPI)
Fig. 3
Fig. 3
68-year-old patient in the 2nd year of the follow-up after radical cystectomy with local recurrence und restaging with PET/CT scan. The PET/CT scan reveals multiple enlarged abdominal lymph node metastases, i.e., mesenteric lymph node metastases, which are only [68 Ga]FAPI-avid (d–f) [68 Ga]FAPI-SUVmax 10,11 vs. [18F]FDG-SUVmax 3,16) (red arrow = FAPI)
Fig. 4
Fig. 4
Intraindividual comparison of [18F]FDG and [68Ga]FAPI in a 65-year-old patient presenting with a strong [68 Ga]FAPI uptake in retroperitoneal/paraaortal ([68Ga]FAPI-SUVmax 12,0 vs. [18F]FDG-SUVmax 10,42) and pelvic metastatic lymph nodes ([68Ga]FAPI-SUVmax 15,28 vs. [18F]FDG-SUVmax 8,89) while only mild to moderate uptake on [18F]FDG PET/CT. The low [68Ga]FAPI uptake in normal organs and excellent tumor-to-background ratio lead to significantly better delineation of tumor lesions (black arrow) ([68Ga]FAPI-SUVmax 8,16 vs. [18F]FDG-SUVmax 3,86) (green arrow = [18F]FDG, red arrow = [68Ga]FAPI)
Fig. 5
Fig. 5
The depiction of overall metastatic lesions in a box-plot, FAPI vs. FDG
See this image and copyright information in PMC

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