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Multimodal [¹⁸ F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNF? Transgenic Mice.

ABSTRACT: In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([¹⁸ F]FDG) and [¹⁸ F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [¹⁸ F]FDG, for detecting inflammatory processes, or [¹⁸ F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV_mean ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [¹⁸ F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [¹⁸ F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [¹⁸ F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

SUBMITTER: Hayer S

PROVIDER: S-EPMC6852546 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Multimodal [18 F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice.

Hayer Silvia S Zeilinger Markus M Weiss Volker V Dumanic Monika M Seibt Markus M Niederreiter Birgit B Shvets Tetyana T Pichler Florian F Wadsak Wolfgang W Podesser Bruno K BK Helbich Thomas H TH Hacker Marcus M Smolen Josef S JS Redlich Kurt K Mitterhauser Markus M

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20190730 9

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18 F]FDG) and [18 F]fluoride µPET/CT imaging to monitor systemic inflammator ...[more]

PMID: 31063606

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Project description:Knowledge of the within-subject variability of 18F-FDG PET/MRI measurements is necessary for proper interpretation of quantitative PET or MRI metrics in the context of therapeutic efficacy assessments with integrated PET/MRI scanners. The goal of this study was to determine the test-retest repeatability of these metrics on PET/MRI, with comparison to similar metrics acquired by PET/CT. Methods: This prospective study enrolled subjects with pathology-proven pelvic malignancies. Baseline imaging consisted of PET/CT immediately followed by PET/MRI, using a single 370-MBq 18F-FDG dose. Repeat imaging was performed within 7 d using an identical imaging protocol, with no oncologic therapy between sessions. PET imaging on both scanners consisted of a list-mode acquisition at a single pelvic station. The MRI consisted of 2-point Dixon imaging for attenuation correction, standard sequences for anatomic correlation, and diffusion-weighted imaging. PET data were statically reconstructed using various frame durations and minimizing uptake time differences between sessions. SUV metrics were extracted for both PET/CT and PET/MRI in each imaging session. Apparent diffusion coefficient (ADC) metrics were extracted for both PET/MRI sessions. Results: The study cohort consisted of 14 subjects (13 female, 1 male) with various pelvic cancers (11 cervical, 2 rectal, 1 endometrial). For SUVmax, the within-subject coefficient of variation (wCV) appeared higher for PET/CT (8.5%-12.8%) than PET/MRI (6.6%-8.7%) across all PET reconstructions, though with no significant repeatability differences (all P values ≥ 0.08) between modalities. For lean body mass-adjusted SUVpeak, the wCVs appeared similar for PET/CT (9.9%-11.5%) and PET/MRI (9.2%-11.3%) across all PET reconstructions, again with no significant repeatability differences (all P values ≥ 0.14) between modalities. For PET/MRI, the wCV for ADCmedian of 3.5% appeared lower than the wCVs for SUVmax (6.6%-8.7%) and SULpeak (9.2%-11.3%), though without significant repeatability differences (all P values ≥ 0.23). Conclusion: For solid tumors of the pelvis, the repeatability of the evaluated SUV and ADC metrics on 18F-FDG PET/MRI is both acceptably high and similar to previously published values for 18F-FDG PET/CT and MRI, supporting the use of 18F-FDG PET/MRI for quantitative oncologic treatment response assessments.

Project description:BackgroundMagnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center.MethodsPatients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM.ResultsA total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively.Conclusions18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.

Project description:PurposeThis study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies.MethodsA total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated.ResultsA total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05).Conclusion[18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.

Project description:Backgroundsignificance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma.MethodsWe retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org).ResultsWe identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (=?0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity.Conclusions[18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology.

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Multimodal [¹⁸ F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNF? Transgenic Mice.

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Multimodal [<sup>18</sup> F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice.

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Multimodal [18 F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNF? Transgenic Mice.

Publications

Multimodal [<sup>18</sup> F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Multimodal [¹⁸ F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNF? Transgenic Mice.