F-18 FDG PET/CT in Relapsing Polychondritis Patients with Initial Respirotory Symptoms: Imaging Features and Association with Pulmonary Function and Disease Activity

Background: To summarize F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging features of relapsing polychondritis (RP) and to evaluate the feasibility of imaging parameters in the estimation of pulmonary function and disease activity in a cohort of RP patients with airway involvement.Methods: Thirty RP patients with respiratory symptoms who underwent PET/CT scans before corticosteroid treatment were included. Six patients underwent another post-therapeutic PET/CT scan. Imaging features were described by consensus, and FDG uptake values (SUVmax, PET FDG Burden Score (PETFBS) and PETCTindex) either for global cartilages or for the airway were calculated to correlate with clinical symptoms, pulmonary functional parameters and serological inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).Results: Laryngo-tracheo-bronchial involvement was detected by PET/CT for all patients with increased FDG uptake in 28/30 patients. The incidence of positive PET was higher in segments with wall thickening (52.68% vs. 15.48%) but was not associated with calcification or stenosis. A total of 46.7% (14/30) of patients presented with sole respiratory symptoms, while PET/CT revealed additional abnormalities in addition to laryngo-tracheo-bronchia. FDG uptake values negatively correlated with disease duration but not with fever. All FDG uptake values showed a positive correlation with FEV1/FVC, with the highest coefficient for SUVmax in the airway (rs =0.628). CRP and ESR were negatively correlated with PETFBS and PETCTindex but not with SUVmax. The largest Spearman correlation coefficient resulted in PETFBS in the airway (rs =0.67). Re-examination PET/CT in 6 patients revealed partial therapeutic response (n = 4), stable disease (n = 1) and progressive disease (n = 1).Conclusion: PET/CT is a valuable tool for assessing RP with airway involvement, especially for patients who present with sole respiratory symptoms. SUVmax and PETFBS have distinct advantages in the clinical evaluation of RP with respect to pulmonary function and disease activity.

Multi-parametric PET/MRI With FDG and RGD for Enhanced Tumor Characterization of Patients With Cervical Cancer

Aim: The concept of personalized medicine has brought increased awareness to the importance of inter- and intra-tumor heterogeneity for cancer treatment. The aim of this study was to explore simultaneous multi-parametric PET/MRI prior to chemoradiotherapy for cervical cancer for characterization of tumors and tumor heterogeneity. Methods: Ten patients with histologically proven primary cervical cancer were examined with multi-parametric 68Ga-NODAGA-E[c(RGDyK)]2-PET/MRI for radiation treatment planning after diagnostic 18F-FDG-PET/CT. Standardized uptake values (SUV) of RGD and FDG, diffusion weighted MRI and the derived apparent diffusion coefficient (ADC), and pharmacokinetic maps obtained from dynamic contrast-enhanced MRI with the Tofts model (iAUC60, Ktrans, ve, and kep) were included in the analysis. The spatial relation between functional imaging parameters in tumors was examined by a correlation analysis and joint histograms at the voxel level. The ability of multi-parametric imaging to identify tumor tissue classes was explored using an unsupervised 3D Gaussian mixture model-based cluster analysis.Results: Functional MRI and PET of cervical cancers appeared heterogeneous both between patients and spatially within the tumors, and the relations between parameters varied strongly within the patient cohort. The strongest spatial correlation was observed between FDG uptake and ADC (median r=-0.7). There was moderate voxel-wise correlation between RGD and FDG uptake, and weak correlations between all other modalities. Distinct relations between the ADC and RGD uptake as well as the ADC and FDG uptake were apparent in joint histograms. A cluster analysis using the combination of ADC, FDG and RGD uptake suggested tissue classes which could potentially relate to tumor sub-volumes. Conclusion: A multi-parametric PET/MRI examination of patients with cervical cancer integrated with treatment planning and including estimation of angiogenesis and glucose metabolism as well as MRI diffusion and perfusion parameters is feasible. A combined analysis of functional imaging parameters indicates a potential of multi-parametric PET/MRI to contribute to a better characterization of tumor heterogeneity than the modalities alone. However, the study is based on small patient numbers and further studies are needed prior to the future design of individually adapted treatment approaches based on multi-parametric functional imaging.

Phenotyping Type 2 Diabetes in Terms of Myocardial Insulin Resistance and Its Potential Cardiovascular Consequences: A New Strategy Based on 18F-FDG PET/CT

Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. Methods: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic–euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81–44.06] vs. 30.82 [21.48–38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D.

Ringed Fluorodeoxyglucose Uptake Predicted Poor Prognosis After Resection of Pulmonary Pleomorphic Carcinoma

Background:Pulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection.Methods:We retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors.Results:Overall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p=0.003), a cavity in the tumor on CT (p=0.004), and tumor size (>40mm) (p=0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p=0.002), a cavity on CT (p<0.001), tumor size (p=0.007), and pleural invasion (p=0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor. Conclusion:Early relapse was frequently observed. This study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis. Trial registration:The study was approved by the Kobe City Medical Center General Hospital’s ethics board (No. 20112) on August 20, 2020.

Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients: a pilot study

Purpose To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers — SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs — were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.