Increased Pituitary Fluorine-18-Fluorodeoxyglucose Uptake in Patients with Differentiated Thyroid Cancer in Hypothyroidism versus under Recombinant Human Thyroid-Stimulating Hormone Stimulation.

The incidental pituitary hypermetabolism on 18F-FDG PET/CT should be further evaluated for discriminating between pathologic and physiologic uptake, but a recent study suggests that pituitary hypermetabolism is common in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid hormone withdrawal (THW). The aim of this retrospective study was to compare pituitary metabolism in patients with DTC undergoing 18F-FDG PET/CT under THW versus recombinant human thyroid-stimulating hormone (rhTSH) stimulation. We confirmed a higher pituitary SUVmax and SUVratio with a higher prevalence of pituitary hypermetabolism in the THW group compared to the rhTSH group. A positive correlation between serum TSH levels and pituitary SUVmax was observed only in the THW group. The present findings support the hypothesis that pituitary hypermetabolism on 18F-FDG PET/CT in patients with DTC undergoing THW is a common physiological response to hypothyroidism. Awareness of this physiological hypermetabolism is important to avoid potential pitfalls in image interpretation that could trigger unnecessary investigations

Performance of 18F-FET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: systematic review and meta-analysis.

For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET. We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria. Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11). For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances

Increased ¹⁸F-FDG signal recovery from small physiological structures in digital PET/CT and application to the pituitary gland.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in <sup>18</sup> F-FDG imaging. We compared the physiological <sup>18</sup> F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2-20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0-5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher <sup>18</sup> F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new "higher" SUV of the normal <sup>18</sup> F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis

Imaging of ανβ3 integrin expression in rheumatoid arthritis with [68Ga]Ga-NODAGA-RGDyk PET/CT in comparison to [18F]FDG PET/CT

[Ga-68] Ga-NODAGA-RGDyk PET/CT and [F-18] FDG PET/CT were performed in a 65-year-old woman during the work-up of a squamous cell carcinoma of the tongue within a clinical study protocol. Images revealed both tracers' uptake in the primary tumor and cervical lymph nodes, but also bilaterally in the shoulders, elbows, wrists, metacarpophalangeal, interphalangeal, and hip joints. The patient had been diagnosed with rheumatoid arthritis 8 years prior to the examination. Images showed a significantly higher [F-18] FDG than [Ga-68] Ga-NODAGA-RGDyk uptake in primary tumor and cervical lymph nodes. However, the patient with moderately active rheumatoid arthritis had similar levels of [Ga-68]Ga-NODAGA-RGDyk and [F-18] FDG uptake in the involved joints, but with no [Ga-68] Ga-NODAGA-RGDyk uptake in the surrounding muscles, unlike with [F-18]FDG. Our case suggests that [Ga-68]Ga-NODAGA-RGDyk PET/CT allows imaging of integrins expression in rheumatoid arthritis, including integrins expressed in synovial angiogenesis, with potentially a better signal-to-noise ratio than on [F-18]FDG PET/CT. (C) 2021 The Author(s). Published by Elsevier Masson SAS

Imaging angiogenesis in atherosclerosis in large arteries with 68Ga-NODAGA-RGD PET/CT: relationship with clinical atherosclerotic cardiovascular disease.

Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of <sup>68</sup> Ga-NODAGA-RGD, a specific α <sub>v</sub> β <sub>3</sub> integrin ligand for PET. The data of 44 patients who underwent <sup>68</sup> Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann-Whitney U test, Pearson correlation and Spearman correlation. <sup>68</sup> Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03-2.55] vs. 1.81 [1.56-1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). <sup>68</sup> Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis

Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases.

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team

Signature of survival: a ¹⁸F-FDG PET based whole-liver radiomic analysis predicts survival after ⁹⁰Y-TARE for hepatocellular carcinoma.

To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 ( <sup>90</sup> Y-TARE) for unresectable hepatocellular carcinoma (uHCC). The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; <i>P</i> = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; <i>P</i> = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore ( <i>P</i> = 0.006) and OS-pPET-RadScore ( <i>P</i> = 0.001) as independent negative predictors. Pretreatment <sup>18</sup> F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing <sup>90</sup> Y-TARE for uHCC. Pretreatment <sup>18</sup> F-FDG PET of 47 consecutive patients undergoing <sup>90</sup> Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis

Voxel-based 18F-FET PET segmentation and automatic clustering of tumor voxels: A significant association with IDH1 mutation status and survival in patients with gliomas.

Aim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas. Thirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates. Twenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04). Based on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas

Diagnostic Performance of PET or PET/CT Using ¹⁸F-FDG Labeled White Blood Cells in Infectious Diseases: A Systematic Review and a Bivariate Meta-Analysis.

Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose ( <sup>18</sup> F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic. A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) of <sup>18</sup> F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated. Eight studies on the use of <sup>18</sup> F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75-92.9%], specificity 92% (95%CI 79.8-97.1%), LR+ 6.6 (95%CI: 3.1-14.1), LR- 0.2 (95%CI: 0.12-0.33), DOR 43.5 (95%CI: 12.2-155). A statistically significant heterogeneity was not detected. Despite limited literature data, <sup>18</sup> F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed