[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04

Hu, Kongzhen; Wang, Lijuan; Wu, Hubing; Huang, Shun; Tian, Ying; Wang, Qiaoyu; Chen, Xiao; Han, Yanjiang; Tang, Ganghua

doi:10.1007/s00259-021-05646-z

Cited by 72 publications

(52 citation statements)

References 31 publications

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“…The correlation coefficients of 68 Ga-FAPI PET and MRI remained relatively stable when different acquisition time points for 68 Ga-FAPI PET were compared. Several previous studies have analysed different 68 Ga-FAPI PET acquisition time points ranging from 10 min to 3 h for various tumour entities, including ACC, and found decreasing signal intensities but increasing tumour-to-background ratios (TBR) over time, so that the optimal imaging time point for 68 Ga-FAPI PET is still a point of discussion [ 16 , 26 , 27 , 28 , 29 ]. In our dataset, 68 Ga-FAPI PET signal intensities decreased over time, too, while the correlations of 68Ga-FAPI PET images with MRI sequences were mostly stable when comparing PET acquisition at 10, 60 and 180 min p.i.…”

Section: Discussionmentioning

confidence: 99%

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences

Liew

Röhrich

Loi

et al. 2022

Cancers

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Background: Fibroblast Activation Protein (FAP) is a new target for positron emission tomography and computed tomography (PET/CT) imaging of epithelial tumours embedded in a fibrous stroma. Adenoid cystic carcinomas (ACCs) have shown elevated tracer uptake in 68Gallium (68Ga)-labelled FAPIs in previous studies. The current gold standard for ACC imaging is contrast-enhanced (ce) MRI, where intertumoural heterogeneity leads to variable appearance on T1-weighted (T1w) and T2-weighted (T2w) images. In this retrospective analysis, we correlated 68Ga-FAPI PET signalling at three time points with ceT1w and T2w MRI signals to further characterise the significance of 68Ga-FAPI uptake in ACCs. Methods: Clinical PET/CT scans of 12 ACC patients were performed at 10, 60 and 180 min post i.v. administration of 68Ga-labelled-FAPI tracer molecules. 68Ga-PET- and corresponding MRI-scans were co-registered, and 3D volumetric segmentations were performed on ceT1w and T2w lesions of co-registered MRI slides. Signal intensity values of 68Ga-FAPI PET signalling and ceT1w/T2w MRI scans were analysed for their pixelwise correlation in each patient. Pooled estimates of the correlation coefficients were calculated using the Fisher z-transformation. Results: 68Ga-FAPI PET signals showed a very weak positive correlation with ceT1w values (pooled correlation 0.114, 0.147 and 0.162 at 10, 60 and 180 min) and a weak negative correlation with T2w values (pooled correlation −0.148, −0.121 and −0.225 at 10, 60 and 180 min). Individual r-values at 60 min ranged from −0.130 to 0.434 in ceT1w and from −0.466 to 0.637 in T2w MRI scans. Conclusion: There are only slight correlations between the intensity of 68Ga-FAPI PET signals and tumour appearance in ceT1w or T2w MRI scans, which underlines that 68Ga-FAPI PET signalling is not a surrogate marker of MRI sequences but an independent signal.

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Section: Discussionmentioning

confidence: 99%

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences

Liew

Röhrich

Loi

et al. 2022

Cancers

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“…18 F-NOTA-FAPI-04 ( 18 F-FAPI-42) was obtained by replacing the DOTA with chelator NOTA in FAPI-04 and Aqueous 18 F-Labeling by the Al 18 F chelation technique ( 21 , 40 ). 18 F-FAPI-42 was initially used to diagnose lung, pancreatic, colorectal, prostate, and lymphoma and was compared with 18 F-FDG ( 21 ).…”

Section: Targeting Cafs For Imagingmentioning

confidence: 99%

“…The results showed that the excretion route of 18 F-FAPI-42 was mainly in the urinary and biliary systems, similar to the previously reported tracers 18 F-FAPI-74, 68 Ga-FAPI-04, and 68 Ga-FAPI-46; compared with 18 F-FDG imaging, 18 F-FAPI-42 had lower SUVmean in the liver, brain, spleen, and bone marrow; in addition, 18 F-FAPI-42 bone uptake was low, indicating that this tracer was not defluorinated at the time of detection. Another study including a total of 22 patients with hepatocellular carcinoma, lung cancer, colorectal cancer, gastric cancer, esophageal cancer, cheek carcinosarcoma, abdominal neuroendocrine carcinoma, and clear cell carcinoma of the bladder conducted a human biodistribution study of 18 F-FAPI-42 and compared it with 68 Ga-FAPI-04 ( 40 ). Data from this study showed that the optimal image acquisition time for 18 F-FAPI-42 was 1 h after injection; 68 Ga-FAPI-42 showed higher physiological uptake in the parotid, salivary gland, thyroid, and pancreas compared with 68 Ga-FAPI-04; both had equal detection rates for lesions; in addition, 18 F-FAPI-42 showed higher TBRs in the liver, bone, lymph nodes, pleura, and peritoneal metastases.…”

Section: Targeting Cafs For Imagingmentioning

confidence: 99%

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

Huang

et al. 2022

Front. Oncol.

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Fibroblast activation protein (FAP), a type II transmembrane serine protease, is highly expressed in more than 90% of epithelial tumors and is closely associated with various tumor invasion, metastasis, and prognosis. Using FAP as a target, various FAP inhibitors (FAPIs) have been developed, most of which have nanomolar levels of FAP affinity and high selectivity and are used for positron emission tomography (PET) imaging of different tumors. We have conducted a systematic review of the available data; summarized the biological principles of FAPIs for PET imaging, the synthesis model, and metabolic characteristics of the radiotracer; and compared the respective values of FAPIs and the current mainstream tracer 18F-Fludeoxyglucose (18F-FDG) in the clinical management of tumor and non-tumor lesions. Available research evidence indicates that FAPIs are a molecular imaging tool complementary to 18F-FDG and are expected to be the new molecule of the century with better imaging effects than 18F-FDG in a variety of cancers, including gastrointestinal tumors, liver tumors, breast tumors, and nasopharyngeal carcinoma.

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“…Differences in the biodistribution of [ 18 F]FAPi-42 and [ 68 Ga]Ga-FAPi-04 in normal organs might be due to the different lipophilicity of the NOTA-chelator and DOTA-chelator groups. This might influence the detection of lesions in specific regions, especially for pancreatic, gallbladder, and biliary tract tumors [20]. Drug-related pharmacologic effects or physiologic responses have so farnever been observed in clinical studies, implying the use of FAP inhibitors for PET imaging.…”

Section: Developing Pet Radiopharmaceuticalsmentioning

confidence: 99%

Imaging Cancer-Associated Fibroblasts (CAFs) with FAPi PET

et al. 2022

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The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on the cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have recently been developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments regarding radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors, such as primary liver and gastro-entero-pancreatic cancer, or in regions with an unfavorable tumor-to-background ratio at FDG-PET/CT (i.e., brain), and in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at present, and definitive conclusions about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center prospective studies powered for efficacy are needed.

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[18F]FAPI-42 PET imaging in cancer patients: optimal acquisition time, biodistribution, and comparison with [68Ga]Ga-FAPI-04

Cited by 72 publications

References 31 publications

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences

FAP-Specific Signalling Is an Independent Diagnostic Approach in ACC and Not a Surrogate Marker of MRI Sequences

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

Imaging Cancer-Associated Fibroblasts (CAFs) with FAPi PET

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