FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study
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SUBMITTER: Kastrati K
PROVIDER: S-EPMC11019096 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Project description:Despite revolutionizing the field of oncological imaging, Positron Emission Tomography (PET) with [18F]Fluorodeoxyglucose (FDG) as its workhorse is limited by a lack of specificity and low sensitivity in certain tumor subtypes. Fibroblast activation protein (FAP), a type II transmembrane glycoprotein, is expressed by cancer-associated fibroblasts (CAFs) that form a major component of the tumor stroma. FAP holds the promise to be a pan-cancer target, owing to its selective over-expression in a vast majority of neoplasms, particularly epithelial cancers. Several radiolabeled FAP inhibitors (FAPI) have been developed for molecular imaging and potential theranostic applications. Preliminary data on FAPI PET/CT remains encouraging, with extensive multi-disciplinary clinical research currently underway. This review summarizes the existing literature on FAPI PET/CT imaging with an emphasis on diagnostic applications, comparison with FDG, pitfalls, and future directions.
| S-EPMC10297281 | biostudies-literature
Project description:Fibroblast-activation protein (FAP) is a serine protease classified in the dipeptidyl peptidase 4 (DPP4) family. FAP is predominantly expressed in activated fibroblasts such as the cancer-associated fibroblasts (CAFs). FAP expression in CAFs is associated with tumor progression and poor prognosis in solid cancers. Recently, radiolabeled FAP inhibitors (FAPI) has been developed, which enables positron emission tomography (PET) imaging of FAP. FAPI PET/CT can provide a higher tumor-to-background ratio (TBR) than 18F-fludeoxyglucose PET/CT in various cancers, and thus has attracted substantial attention. As studies on FAPI PET grow in number and size, incidental findings related to non-oncologic conditions have been increasingly reported. FAPI PET uptake has been reported in various conditions such as benign tumors, fibrotic, granulomatosis, scarring/wound, degenerative diseases, and inflammatory diseases.The knowledge of physiological and non-oncologic causes of FAPI uptake is indispensable for accurate FAPI PET/CT interpretation and can help appropriate management of incidental findings on FAPI PET/CT in patients referred for cancer staging indications. In this review article, we describe for each organ system (Brain, Oral mucosa, Salivary Glands, Thyroid, Lung, Myocardium, Breast, Esophagus, Stomach, Intestine, Liver, Gallbladder, Pancreas, Spleen, Kidney, , Uterus, Bone marrow, Joints, Muscle, Vessels, Lymph nodes), the patterns of physiological FAPI uptake and the main causes of non-oncological uptake reported from the literature with FAPI-02, FAPI-04 and FAPI-46. We also illustrate some examples from our institutional database at UCLA.
| S-EPMC9975522 | biostudies-literature
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.
| S-EPMC8717183 | biostudies-literature
Project description:Purpose68Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer 18F-FDG was performed in selected cases.Patients and methodsA total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent 68Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional 18F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group.ResultsIn 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in 68Ga-FAPI compared to 18F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of 68Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to 18F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed.ConclusionDue to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than 18F-FDG-PET/CT, 68Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.
| S-EPMC8484099 | biostudies-literature
Project description: Not available
| S-EPMC10413291 | biostudies-literature
Project description:Cancer-associated fibroblasts that overexpress fibroblast activation protein (FAP) are enriched in many epithelial carcinomas and in hematologic neoplasms. PET/CT with radiolabeled FAP inhibitor (FAPI) is a new diagnostic tool for visualizing the tumor stroma. This prospective study aimed to profile FAPs in different subtypes of lymphomas and explore the potential utility of 68Ga-FAPI PET/CT in lymphomas. Methods: In this prospective study, we recruited 73 lymphoma patients who underwent 68Ga-FAPI PET/CT and recorded and measured semiquantitative parameters and ratios of their scan results. FAPI expression was assessed by immunochemistry in samples obtained from 22 of the lymphoma patients. Results: We evaluated 11 patients with Hodgkin lymphoma and 62 with non-Hodgkin lymphoma (NHL). Significantly elevated FAP uptake was observed in Hodgkin lymphoma lesions, correlating with the intensity of FAP immunostaining (score, 3+). A positive association was found between the corresponding clinical classification of NHL and the 68Ga-FAPI uptake activity of the lesion. Aggressive NHL lesions, with moderate to strong FAP immunostaining (score, 2+ to 3+), exhibited intense to moderate 68Ga-FAPI uptake. Indolent NHL lesions showed weak FAP staining and mild to moderate 68Ga-FAPI uptake. No statistically significant correlation emerged between the sum of the product of the diameters and the corresponding SUVmax (P = 0.424). The tumor-to-liver ratios were 6.26 ± 4.17 in indolent NHL and more than 9 in other subtypes. Conclusion: 68Ga-FAPI imaging can be used to detect FAP expression in lymphoma lesions and may be an alternate method for characterizing lymphoma profiles.
| S-EPMC8805784 | biostudies-literature
Project description:This study aims to further explore dynamic 68Ga-FAPI-04 PET/CT imaging of healthy Chinese subjects and lung cancer patients. Moreover, the variability of 68Ga-FAPI-04 uptake in normal organs was measured to provide a basis for analyzing its biological distribution, interpreting auxiliary images, determining the reliability of image quantification, and monitoring treatment. Six patients (3 subjects without tumors and 3 lung cancer patients) separately underwent 68Ga-FAPI-04 and 2-[18F]FDG PET/CT imaging within 1 week. The biodistribution and internal radiation dosimetry were reported and compared with data previously obtained from Caucasian patients. Moreover, the mean SUV (standardized uptake value) was normalized to body mass or to lean body mass (SUL), and the coefficients of variation (CVs) were calculated and compared for each volume of interest. The average whole-body effective dose was calculated to be 1.27E-02 mSv/MBq, which was comparable with previously reported results of 68Ga-FAPI-04 probes. Furthermore, the SUVmean was slightly higher than the SULmean in most organs; however, the CV of the SULmean for most organs was higher than that of the SUVmean at later time points. In the liver, the CV of the SUVmean was lower (12.7%) than that of the SULmean and was similar to the CV for corresponding 2-[18F]FDG PET/CT value (11.8%). In addition, 68Ga-FAPI-04 PET/CT showed good efficacy for diagnosing lung cancer patients in this study. A comparison of the radiation dosimetry obtained before from a Caucasian population demonstrated no clinically significant differences between these two populations after 68Ga-FAPI-04 injection. The variability in most organs was slightly lower for SUVmean than for SULmean, suggesting that SUVmean may be the preferable parameter for quantifying images obtained with 68Ga-FAPI-04. In addition, 68Ga-FAPI-04 PET/CT imaging is expected to be a promising tool for diagnosing lung cancer.
| S-EPMC7991833 | biostudies-literature
Project description:Background/objectivesTo evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort.MethodsPatients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth.Results63 FAPI scans were performed in 64 patients enrolled (26 May 2022-30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N (p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG.ConclusionsIn a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial's conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.
| S-EPMC11597145 | biostudies-literature
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.
| S-EPMC11405641 | biostudies-literature
Project description:Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)]. Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.
| S-EPMC7946849 | biostudies-literature