Novel 68Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.
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ABSTRACT:
SUBMITTER: Demmert TT
PROVIDER: S-EPMC10071804 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Novel <sup>68</sup>Ga-FAPI PET/CT Offers Oncologic Staging Without COVID-19 Vaccine-Related Pitfalls.
Demmert Tristan T TT Maric Ines I Pomykala Kelsey L KL Lueckerath Katharina K Siveke Jens J Schaarschmidt Benedikt M BM Hamacher Rainer R Herrmann Ken K Fendler Wolfgang P WP
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20221117 3
In the setting of ongoing coronavirus disease 2019 vaccination, vaccine-related tracer uptake in locoregional lymph nodes has become a well-known issue in tumor staging by <sup>18</sup>F-FDG PET/CT. <sup>68</sup>Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT is a new oncologic imaging tool that may overcome this limitation. <b>Methods:</b> We assessed postvaccine head-to-head and same-day <sup>18</sup>F-FDG and <sup>68</sup>Ga-FAPI-46 PET/CT findings in a series of 11 patients from a l ...[more]
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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: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: Not available
| S-EPMC10413291 | 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
Project description:BackgroundAdenoid cystic carcinomas (ACCs) are rare epithelial tumors mostly situated in the head and neck region and characterized by infiltrative growth. The tumor stroma of ACCs includes cancer-associated fibroblasts (CAFs) expressing Fibroblast Activation Protein (FAP), a new target for positron emission tomography (PET) imaging. Here we describe the value of PET/ computed tomography (PET/CT) imaging using 68Ga-labelled FAP-Inhibitors (68Ga-FAPI-PET/CT) and their clinical potential for staging and radiotherapy planning in 12 ACC patients (7 primary, 5 recurrent).Patients and methodsPatients underwent contrast enhanced staging CT (ceCT) and magnetic resonance imaging (ceMRI) before 68Ga-FAPI - PET/CT. PET-scans were acquired 10, 60 and 180 minutes after administration of 150-250 MBq of 68Ga-labelled FAPI tracers. SUVmax and SUVmean values of ACCs and healthy organs were obtained using a 60% of maximum iso-contour. FAP and alpha smooth muscle actin (α-SMA) immunohistochemistry was performed in 13 cases (3 with and 10 without 68Ga FAPI-PET/CT). Staging and radiotherapy planning based on 68Ga-FAPI-PET/CT versus ceCT/MRI alone were compared.ResultsWe observed elevated tracer uptake in all ACCs. Immunohistochemistry showed FAP-expressing CAFs in the tumor. Compared to conventional staging, 68Ga-FAPI-PET/CT led to upstaging in 2/12 patients and to detection of additional metastases in 3 patients, thus in total 42% of patients had their staging altered. Moreover, 68Ga-FAPI PET improved the accuracy of target volume delineation for radiotherapy, as compared to CT and MRI.Conclusion68Ga-FAPI-PET/CT is a promising imaging modality for ACC, increasing the accuracy of staging exams and radiotherapy planning volumes, as compared conventional to CT and MRI.
| S-EPMC9913884 | biostudies-literature
Project description:Background/Objectives: Over the past four years, 68Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) has been established at a tertiary cancer care facility in Jordan. This retrospective study aims to explore tracer uptake metrics across various epithelial neoplasms, identify diagnostic pitfalls associated with 68Ga-FAPI PET/CT, and evaluate the influence of 68Ga-FAPI PET/CT staging results on changes in therapeutic intent compared to gold standard molecular imaging modalities. Methods: A total of 48 patients with biopsy-confirmed solid tumors underwent 77 68Ga-FAPI PET/CT examinations for molecular imaging assessment, encompassing neoplasms originating from the gastrointestinal tract, head and neck, hepatobiliary system, pancreas, breast, and lung. Results: Notably, pancreaticobiliary tumors exhibited the highest tracer uptake, with mean maximum standardized uptake values (SUVmax) and tumor-to-background ratios (TBR) surpassing 10. A comparative sub-analysis of 68Ga-FAPI PET metrics in 20 treatment-naïve patients revealed a significant correlation between 68Ga-FAPI uptake metrics and tumor grade (Spearman's rho 0.83; p = 0.00001). Importantly, the results from 68Ga-FAPI PET/CT influenced treatment decisions in 35.5% of the cases, primarily resulting in an escalation of management plans. A total of 220 diagnostic challenges were identified across 88.3% of the scans, predominantly within the musculoskeletal system, attributed to degenerative changes (99 observations). Conclusions: This comprehensive analysis highlights the potential significance of 68Ga-FAPI PET/CT in oncological imaging and treatment strategy, while also emphasizing the necessity for meticulous interpretation to mitigate diagnostic challenges.
| S-EPMC11764383 | biostudies-literature
Project description:Purpose68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage.MethodsTwelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated.ResultsFocal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02).ConclusionWe demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.
| S-EPMC8940837 | biostudies-literature
Project description:PurposeMyocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF.MethodsIn this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated.Results[68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage.ConclusionsWe present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.
| S-EPMC10119041 | 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