Dataset Information

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

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.

SUBMITTER: Giesel FL

PROVIDER: S-EPMC8566651 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Giesel Frederik L FL Kratochwil Clemens C Schlittenhardt Joel J Dendl Katharina K Eiber Matthias M Staudinger Fabian F Kessler Lukas L Fendler Wolfgang P WP Lindner Thomas T Koerber Stefan A SA Cardinale Jens J Sennung David D Roehrich Manuel M Debus Juergen J Sathekge Mike M Haberkorn Uwe U Calais Jeremie J Serfling Sebastian S Buck Andreas L AL

European journal of nuclear medicine and molecular imaging 20210617 13

<h4>Purpose</h4>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 <sup>68</sup>Ga-FAPI versus standard-of-care <sup>18</sup>F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.<h4>Material and methods</h4>This international retrospective multicenter analysis include ...[more]

PMID: 34137945

Similar Datasets

Project description:Aim/purposeFibroblast 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 methodsThis 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.ResultsOverall, 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.

Project description:ObjectiveThe present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs).Materials and methodsFifty-six patients (age: 18-80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student's t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities.Results68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT.Conclusion68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Project description:Targeting cancer-associated fibroblasts (CAFs) has become an attractive goal for diagnostic imaging and therapy because they can constitute as much as 90% of a tumor mass. The serine protease fibroblast activation protein (FAP) is overexpressed selectively in CAFs, drawing interest in FAP as a stromal target. The quinoline-based FAP inhibitor (FAPI) PET tracer 68Ga-FAPI-04 has been previously shown to yield high tumor-to-background ratios (TBRs) in patients with various cancers. Recent developments toward an improved compound for therapeutic application have identified FAPI-46 as a promising agent because of an increased tumor retention time in comparison with FAPI-04. Here, we present a PET biodistribution and radiation dosimetry study of 68Ga-FAPI-46 in cancer patients. Methods: Six patients with different cancers underwent serial 68Ga-FAPI-46 PET/CT scans at 3 time points after radiotracer injection: 10 min, 1 h, and 3 h. The source organs consisted of the kidneys, bladder, liver, heart, spleen, bone marrow, uterus, and remainder of body. OLINDA/EXM software, version 1.1, was used to fit and integrate the kinetic organ activity data to yield total-body and organ time-integrated activity coefficients and residence times and, finally, organ-absorbed doses. SUVs and TBR were generated from the contoured tumor and source-organ volumes. Spheric volumes in muscle and blood pool were also obtained for TBR (tumor SUVmax/organ SUVmean). Results: At all time points, average SUVmax was highest in the liver. Tumor and organ SUVmean decreased over time, whereas TBRs in all organs but the uterus increased. The organs with the highest effective doses were bladder wall (2.41E-03 mSv/MBq), followed by ovaries (1.15E-03 mSv/MBq) and red marrow (8.49E-04 mSv/MBq). The average effective total-body dose was 7.80E-03 mSv/MBq. Conclusion: 68Ga-FAPI-46 PET/CT has a favorable dosimetry profile, with an estimated whole-body dose of 5.3 mSv for an administration of 200 MBq (5.4 mCi) of 68Ga-FAPI-46 (1.56 ± 0.26 mSv from the PET tracer and 3.7 mSv from 1 low-dose CT scan). The biodistribution study showed high TBRs increasing over time, suggesting high diagnostic performance and favorable tracer kinetics for potential therapeutic applications.

Project description:IntroductionAlthoug 18F-FDG positron emission tomography/computed tomography (PET/CT) is widely accepted as a diagnostic tool for detecting digestive cancers, 68Ga-FAPI-04 PET/CT may perform better in detecting gastrointestinal malignancies at an earlier stage. This study aimed to systematically review the diagnostic performance of 68Ga-FAPI-04 PET/CT compared with that of 18F-FDG PET/CT in primary digestive system cancers.MethodsIn this study, a comprehensive search using the PubMed, EMBASE, and Web of Science databases was performed to identify studies that met the eligibility criteria from the beginning of the databases to March 2023. The quality of the relevant studies with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was assessed using the RevMan 5.3 software. Sensitivity and specificity were calculated using bivariate random-effects models, and heterogeneity was assessed with the I2 statistic and meta-regression analysis using the R 4.22 software.ResultsA total of 800 publications were identified in the initial search. Finally, 15 studies comprising 383 patients were included in the analysis. The pooled sensitivity and specificity of 68Ga-FAPI-04 PET/CT were 0.98 (95% CI, 0.94-1.00) and 0.81 (95% CI, 0.23-1.00), whereas those of 18F-FDG PET/CT were 0.73 (95% CI, 0.60-0.84) and 0.77 (95% CI, 0.52-0.95), respectively. 68Ga-FAPI-04 PET/CT performed better for specific tumours, particularly in gastric, liver, biliary tract, and pancreatic cancers. Both imaging modalities had essentially the same diagnostic efficacy in colorectal cancer.Conclusions68Ga-FAPI-04 PET/CT showed a higher diagnostic ability than 18F-FDG PET/CT in terms of diagnosing primary digestive tract cancers, especially gastric, liver, biliary tract, and pancreatic cancers. The certainty of the evidence was high due to the moderately low risk of bias and low concern regarding applicability. However, the sample size of the included studies was small and heterogeneous. More high-quality prospective studies are needed to obtain higher-quality evidence in the future.Systematic review registrationThe systematic review was registered in PROSPERO [CRD42023402892].

Project description:Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

Project description:ObjectivesWe aimed to investigate the role of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT for the initial assessment of gastric cancer and to explore the factors associated with their uptake.MethodsThis study enrolled 62 patients with histopathologically confirmed gastric cancer. We compared the diagnostic performance of [68Ga]FAPI-04, [18F]FDG, and combined dual-tracer PET/CT. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) were also measured, and the factors that influence tracer uptake were analyzed.Results[68Ga]FAPI-04 PET/CT detected more primary lesions (90.3% vs 77.4%, p = 0.008) and peritoneal metastases (91.7% vs 41.7%, p = 0.031) and demonstrated higher SUVmax and TBR values (p < 0.001) of primary lesions compared to [18F]FDG PET/CT. Dual-tracer PET/CT significantly improved the diagnostic sensitivity for the detection of distant metastases, compared with stand-alone [18F]FDG (97.1% vs 73.5%, p = 0.008) or [68Ga]FAPI-04 (97.1% vs 76.5%, p = 0.016) PET/CT. Subsequently, treatment strategies were changed in nine patients following [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT. Nevertheless, [68Ga]FAPI-04 uptake was primarily influenced by the size and invasion depth of the tumor. Both [68Ga]FAPI-04 and [18F]FDG PET/CT showed limited sensitivity for detecting early gastric cancer (EGC) (37.5% vs 25.0%, p > 0.05).ConclusionsIn this initial study, [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT were complementary and improved sensitivity for the detection of distant metastases pre-treatment in gastric cancer and could improve treatment stratification in the future. [68Ga]FAPI-04 had limited efficacy in detecting EGC.Key points• [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT are complementary to each other for improving diagnostic sensitivity in the initial evaluation of distant metastases from gastric cancer. • [68Ga]FAPI-04 PET/CT showed limited sensitivity in detecting EGC. • Need for further validation in a larger multi-centre prospective study.

Dataset Information

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

Purpose

Material and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Purpose

Material and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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