A New Tool for Extracting Static and Dynamic Parameters from [18F]F-DOPA PET/CT in Pediatric Gliomas.

Background/Objectives: PET imaging with [18F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. Methods: In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [18F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [18F]F-DOPA uptake. A total of 73 subjects with treatment-naïve low- and high-grade gliomas, who underwent brain MRI within two weeks of [18F]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. Results: For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357); however, significant differences were observed in tumor slope (p < 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Conclusions: Our framework aids in analyzing [18F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Diagnostic performance of 2-[18F]FDG PET/CT in recurrent differentiated thyroid cancer and elevated antithyroglobulin antibodies: an updated systematic review and bivariate meta-analysis.

PURPOSE: This updated systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT for the detection of recurrent disease in patients with differentiated thyroid cancer (DTC) who have negative 131I whole body scintigraphy and increased antithyroglobulin antibodies (TgAb) levels. METHODS: The current systematic review was carried out following a preset protocol, and the "Preferred Reporting Items for a Systematic Review and Meta-Analysis" served as a guideline for its development and reporting. A comprehensive research of the PubMed/MEDLINE, Embase and Cochrane library databases was conducted until June 2024. RESULTS: Between 2002 and 2023, 13 studies (608 patients) published on this topic were selected. The pooled sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 2-[18F]FDG PET or PET/CT were 84% (95%CI: 78-87%), 82% (95%CI: 78-86%), 72% (95%CI: 67-76%), 90% (95%CI: 87-93%) and 83% (95%CI: 79%-86%) respectively. The pooled positive and negative likelihood ratios (LR+ and LR - ) and the diagnostic odds ratio (DOR) were 0.180 (95%CI: 0.128-0.253), 3.214 (95%CI: 2.357-4.383), and 17.863 (95%CI: 10.475-30.462), respectively. No statistically significant heterogeneity among the studies was found for all the metrics evaluated (I2 < 50%). CONCLUSIONS: 2-[18F]FDG PET/CT demonstrated a good diagnostic performance in patients with DTC and increased TgAb. Although more studies are warranted, the provided evidence-based data should support the integration of 2-[18F]FDG PET/CT in clinical and diagnostic guidelines on DTC patients with increased TgAb.

Role of 64CuCl2 PET/CT in Detecting and Staging Muscle-Invasive Bladder Cancer: Comparison with Contrast-Enhanced CT and 18F-FDG PET/CT.

Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. 64CuCl2 , a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of 64CuCl2-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and 18F-FDG PET/CT. Methods: We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, 18F-FDG, and 64CuCl2 PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). Results: Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and 64CuCl2 PET/CT showed higher sensitivity than 18F-FDG PET/CT in detecting the primary tumor (P < 0.001); moreover, 64CuCl2 PET/CT was slightly more sensitive than 18F-FDG PET/CT in disclosing soft-tissue lesions (P < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (P < 0.05). On lesion-based analysis, 64CuCl2 PET/CT outperformed 18F-FDG PET/CT and ceCT in detecting disease localizations overall (P < 0.001), in the lymph nodes (P < 0.01), in the skeleton (P < 0.001), and in the soft tissue (P < 0.05). Conclusion: 64CuCl2 PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a "one-stop shop" diagnostic method in these scenarios.

Incidence of subclinical and overt hypothyroidism in children treated with [131I]mIBG: a systematic review and meta-analysis.

INTRODUCTION: Treatment with [131I]mIBG is commonly used in pediatric metastatic neuroblastoma (NB); however, unbound [131I]I might be taken up by the thyroid, causing hypothyroidism. To prevent this occurrence, thyroid blockade with iodine salts is commonly used; despite this precaution, thyroid dysfunction still occurs. This review and meta-analysis aim to clarify the mean frequency of hypothyroidism in children with NB treated with [131I]mIBG and to investigate the possible causes. EVIDENCE ACQUISITION: The literature was searched for English-language scientific manuscripts describing the incidence of TSH elevation and overt hypothyroidism in children with NB treated with [131I]mIBG. Preclinical studies, small-case series, and reviews were excluded. A proportion meta-analysis was conducted to test the influence of potentially relevant factors (type and duration of thyroid blockade, year of the study, sample size) on the incidence of TSH elevation/overt hypothyroidism. EVIDENCE SYNTHESIS: Eleven studies were included. The pooled percentage of TSH elevation was 0.41 (95% CI: 0.27-0.55); the duration of the thyroid blockade (P=0.004) was inversely correlated with the incidence of TSH elevation. Moreover, a TSH increase was more common in patients treated with potassium iodide (KI) alone than in those managed with a multi-drug thyroid blockade (P<0.001). The pooled percentage of children requiring hormone replacement therapy was 0.33 (95% CI: 0.16-0.49). As in the case of TSH elevation, a longer duration of the thyroid blockade (P=0.006) and a multi-pronged approach (P<0.001) were associated with a lower incidence of overt hypothyroidism. CONCLUSIONS: Hypothyroidism appears to occur frequently in children treated with [131I]mIBG, which should be monitored closely after the radionuclide treatment to start hormone replacement therapy as soon as needed. The duration, as well as the type of thyroid blockade, seem to influence the incidence of hypothyroidism; however, more data from prospective evaluations are needed.

Does it work in childhood and adolescence? The predictive role of postoperative/preablative stimulated thyroglobulin levels in paediatric thyroid cancer. A systematic review of the literature.

BACKGROUND: Thyroglobulin is a well-established disease marker during follow-up in paediatric differentiated thyroid cancer. However, no conclusive data on the role of endogenously stimulated thyroglobulin after thyroidectomy (ptTg) in predicting disease-specific outcomes are available. This review aims to establish the prognostic value of ptTg in children with DTC. METHODS: Online medical databases were searched for studies evaluating the association between ptTg and disease-specific outcomes in DTC-affected children. Documents not in English, preclinical studies, other review articles, case reports, and small case series were excluded. The risk of bias was assessed with the QUADAS-2 tool. RESULTS: Twelve studies, analysing 1043 children in total, were included in the review. They all had a retrospective design and were published between 2016 and 2022. Of all patients, 1008 (97%) and 849 (81%) had undergone thyroidectomy and RAI, respectively. Eight studies (756 children) evaluated the correlation between ptTg and disease persistence/relapse: six reported a significant association between these parameters; a specific ptTg cut-off (10-14 ng/ml) was identified at the multivariate analysis in three studies. The remaining four studies assessed the link between ptTg levels and disease extension, with three reporting a correlation between ptTg and lung/nodal metastases. DISCUSSION: ptTg is a readily available and inexpensive parameter, bearing a strong prognostic power in identifying disease persistence, relapse, and the presence of metastases in children affected by DTC.

Reaching the target dose with one single 131 I-mIBG administration in high-risk neuroblastoma: The determinant impact of the primary tumour.

BACKGROUND: 131 I-metaiodobenzylguanidine (131 I-mIBG) effectiveness in children with metastasised neuroblastoma (NB) is linked to the effective dose absorbed by the target; a target of 4 Gy whole-body dose threshold has been proposed. Achieving this dose often requires administering 131 I-mIBG twice back-to-back, which may cause haematological toxicity. In this study, we tried identifying the factors predicting the achievement of 4 Gy whole-body dose with a single radiopharmaceutical administration. MATERIALS AND METHODS: Children affected by metastatic NB and treated with a high 131 I-mIBG activity (>450 MBq (megabecquerel)/kg) were evaluated retrospectively. Kinetics measurements were carried out at multiple time points to estimate the whole-body dose, which was compared with clinical and activity-related parameters. RESULTS: Seventeen children (12 females, median age 3 years, age range: 1.5-6.9 years) were included. Eleven of them still bore the primary tumour. The median whole-body dose was 2.88 Gy (range: 1.63-4.22 Gy). Children with a 'bulky' primary (>30 mL) received a higher whole-body dose than those with smaller or surgically removed primaries (3.42 ± 0.74 vs. 2.48 ± 0.65 Gy, respectively, p = .016). Conversely, the correlation between activity/kg and the whole-body dose was moderate (R: 0.42, p = .093). In the multivariate analysis, the volume of the primary tumour was the most relevant predictor of the whole-body dose (p = .002). CONCLUSIONS: These data suggest that the presence of a bulky primary tumour can significantly prolong the 131 I-mIBG biological half-life, effectively increasing the absorbed whole-body dose. This information could be used to model the administered activity, allowing to attain the target dose without needing a two-step radiopharmaceutical administration.

The evidence-based role of catecholaminergic PET tracers in Neuroblastoma. A systematic review and a head-to-head comparison with mIBG scintigraphy.

BACKGROUND: Molecular imaging is pivotal in staging and response assessment of children with neuroblastoma (NB). [123I]-metaiodobenzylguanidine (mIBG) is the standard imaging method; however, it is characterised by low spatial resolution, time-consuming acquisition procedures and difficult interpretation. Many PET catecholaminergic radiotracers have been proposed as a replacement for [123I]-mIBG, however they have not yet made it into clinical practice. We aimed to review the available literature comparing head-to-head [123I]-mIBG with the most common PET catecholaminergic radiopharmaceuticals. METHODS: We searched the PubMed database for studies performing a head-to-head comparison between [123I]-mIBG and PET radiopharmaceuticals including meta-hydroxyephedrine ([11C]C-HED), 18F-18F-3,4-dihydroxyphenylalanine ([18F]DOPA) [124I]mIBG and Meta-[18F]fluorobenzylguanidine ([18F]mFBG). Review articles, preclinical studies, small case series (< 5 subjects), case reports, and articles not in English were excluded. From each study, the following characteristics were extracted: bibliographic information, technical parameters, and the sensitivity of the procedure according to a patient-based analysis (PBA) and a lesion-based analysis (LBA). RESULTS: Ten studies were selected: two regarding [11C]C-HED, four [18F]DOPA, one [124I]mIBG, and three [18F]mFBG. These studies included 181 patients (range 5-46). For the PBA, the superiority of the PET method was reported in two out of ten studies (both using [18F]DOPA). For LBA, PET detected significantly more lesions than scintigraphy in seven out of ten studies. CONCLUSIONS: PET/CT using catecholaminergic tracers shows superior diagnostic performance than mIBG scintigraphy. However, it is still unknown if such superiority can influence clinical decision-making. Nonetheless, the PET examination appears promising for clinical practice as it offers faster image acquisition, less need for sedation, and a single-day examination.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18 F-fluorodeoxyglucose pattern in a long-known syndrome.

AIM: Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [ 18 F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. METHODS: We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [ 18 F]FDG-PET. The 18 F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. RESULTS: Seven iNPH patients (mean age 74 ±â€…6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism ( P  = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism ( P  = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed ( P  < 0.001 corrected for multiple comparisons). CONCLUSION: In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Does 18F-Fluorocholine PET/CT add value to positive parathyroid scintigraphy in the presurgical assessment of primary hyperparathyroidism?

Introduction: To investigate the value of presurgical 18F-FCH PET/CT in detecting additional hyperfunctioning parathyroids despite a positive 99mTc-sestamibi parathyroid scintigraphy in patients with primary hyperparathyroidism (pHPT). Methods: This is a retrospective study involving patients with pHPT, positive parathyroid scintigraphy performed before 18F-FCH PET/CT, and parathyroid surgery achieved after PET/CT. Imaging procedures were performed according to the EANM practice guidelines. Images were qualitatively interpreted as positive or negative. The number of pathological findings, their topography, and ectopic location were recorded. Histopathology, Miami criterion, and biological follow-up were considered to ensure effective parathyroidectomy confirming the complete excision of all hyperfunctioning glands. The impact of 18F-FCH PET/CT on therapeutic strategy was recorded. Results: 64/632 scanned pHPT patients (10%) were included in the analysis. According to a per lesion-based analysis, sensitivity, specificity, positive predictive value, and negative predictive value of 99mTc-sestamibi scintigraphy were 82, 95, 87, and 93%, respectively. The same values for 18F-FCH PET/CT were 93, 99, 99, and 97%, respectively. 18F-FCH PET/CT showed a significantly higher global accuracy than 99mTc-sestamibi scintigraphy: 98% (CI: 95-99) vs. 91% (CI: 87-94%). Youden Index was 0.79 and 0.92 for 99mTc-sestamibi scintigraphy and 18F-FCH PET/CT, respectively. Scintigraphy and PET/CT were discordant in 13/64 (20%) patients (49 glands). 18F-FCH PET/CT identified nine pathologic parathyroids not detected by 99mTc-sestamibi scintigraphy in 8 patients (12.5%). Moreover, 18F-FCH PET/CT allowed the reconsideration of false-positive scintigraphic diagnosis (scinti+/PET-) for 8 parathyroids in 7 patients (11%). The 18F-FCH PET/CT influenced the surgical strategy in 7 cases (11% of the study population). Conclusion: In a preoperative setting, 18F-FCH PET/CT seems more accurate and useful than 99mTc-sestamibi scan in pHPT patients with positive scintigraphic results. Positive parathyroid scintigraphy could be not satisfactory before neck surgery particularly in patients with multiglandular disease, suggesting a need to evolve the practice and define new preoperative imaging algorithms including 18F-FCH PET/CT at the fore-front in pHPT patients.

Towards an Automated Approach to the Semi-Quantification of [18F]F-DOPA PET in Pediatric-Type Diffuse Gliomas.

BACKGROUND: This study aims to evaluate the use of a computer-aided, semi-quantification approach to [18F]F-DOPA positron emission tomography (PET) in pediatric-type diffuse gliomas (PDGs) to calculate the tumor-to-background ratio. METHODS: A total of 18 pediatric patients with PDGs underwent magnetic resonance imaging and [18F]F-DOPA PET, which were analyzed using both manual and automated procedures. The former provided a tumor-to-normal-tissue ratio (TN) and tumor-to-striatal-tissue ratio (TS), while the latter provided analogous scores (tn, ts). We tested the correlation, consistency, and ability to stratify grading and survival between these methods. RESULTS: High Pearson correlation coefficients resulted between the ratios calculated with the two approaches: ρ = 0.93 (p < 10-4) and ρ = 0.814 (p < 10-4). The analysis of the residuals suggested that tn and ts were more consistent than TN and TS. Similarly to TN and TS, the automatically computed scores showed significant differences between low- and high-grade gliomas (p ≤ 10-4, t-test) and the overall survival was significantly shorter in patients with higher values when compared to those with lower ones (p < 10-3, log-rank test). CONCLUSIONS: This study suggested that the proposed computer-aided approach could yield similar results to the manual procedure in terms of diagnostic and prognostic information.

Diagnostic effectiveness of [18F]Fluoroestradiol PET/CT in oestrogen receptor-positive breast cancer: the key role of histopathology. Evidence from an international multicentre prospective study.

INTRODUCTION: [18F]Fluoroestradiol ([18F]FES) PET/CT has been proposed as a tool for detecting the oestrogen receptor density in patients with metastatic breast cancer (BC) non-invasively across all disease localizations. However, its diagnostic potential in terms of the detection rate (DR) of metastases is unclear. In this study, we pitted this method against [18F]FDG PET/CT and tried to identify predictors of the diagnostic superiority of the [18F] FES-based method. MATERIALS AND METHODS: From a multicentre database, we enrolled all patients with metastatic BC who had undergone both [18F]FES PET/CT and [18F]FDG PET/CT. Two readers assessed both images independently and used a patient-based (PBA) and lesion-based analysis (LBA) to calculate the DR. Pathology-related and clinical factors were tested as predictors of [18F]FES PET/CT superiority using a multivariate model. RESULTS: 92 patients, bearing a total of 2678 metastases, were enrolled. On PBA, the DR of [18F]FDG and [18F]FES PET/CT was 97% and 86%, respectively (p = 0.018). On LBA, the [18F]FES method proved more sensitive than [18F]FDG PET/CT in lymph nodes, bone, lung and soft tissue (p < 0.01). This greater sensitivity was associated with lobular histology, both on PBA (Odds Ratio (OR) 3.4, 95%CI 1.0-12.3) and on LBA (OR 4.4, 95%CI 1.2-16.1 for lymph node metastases and OR 3.29, 95%CI 1.1-10.2 for bone localizations). CONCLUSIONS: The overall DR of [18F]FES PET/CT appears to be lower than that of [18F]FDG PET/CT on PBA. However, the [18F]FES method, if positive, can identify more lesions than [18F]FDG at most sites. The higher sensitivity of [18F]FES PET/CT was associated with lobular histology.

The FDG Pattern of Autonomously Functioning Thyroid Nodules Correlates With Thyroid-Stimulating Hormone and Histopathology.

PURPOSE OF THE REPORT: Whereas the 18 F-FDG PET/CT pattern of malignant thyroid neoplasia is known, the glucose uptake of autonomously functioning thyroid nodules (AFTNs) has not been fully investigated. We aimed to analyze the FDG uptake of AFTNs and its correlation with clinical, laboratory, ultrasonography, and histological features. METHODS: We retrospectively analyzed the records of all AFTN patients from 2 centers, in which an 18 F-FDG PET/CT, thyroid function tests, and neck ultrasound were available within a 3-month window from the thyroid scintigraphy. Forty-five patients (35 female patients; median age, 65 years) were retrospectively included. The presence of FDG uptake was compared with the laboratory data and, whenever available, the histology. RESULTS: Over a 36-month follow-up, 20 patients underwent surgery; 4 cancers, 10 follicular adenomas, and 6 follicular hyperplasias were found. Twenty-two AFTNs (48.9%) were FDG-positive, whereas the remaining 23 (51.1%) were not. Thyroid-stimulating hormone (TSH) was significantly lower in FDG-positive AFTNs than in negative ones (0.055 [0.02-0.42] vs 0.65 [0.2-0.96] mIU/L, P = 0.0018). On multivariate analysis, only TSH was independently associated with FDG uptake ( P = 0.008). On receiver operating characteristic curve analysis, TSH <0.08 mIU/L indicated FDG-positive AFTNs, with 64% sensitivity, 87% specificity, 4.88 positive likelihood ratio, and 0.42 negative likelihood ratio. In histologically proven benign lesions, TSH was significantly lower in follicular adenomas than in follicular hyperplasias ( P < 0.001). Patients with cancer had TSH in the low-normal range. CONCLUSIONS: Autonomously functioning thyroid nodules show heterogeneous uptake FDG pattern, which depends on histopathology and thyroid function. Particularly, follicular adenomas tend to display increased glucose uptake and suppressed TSH.

Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas.

PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

Prognostic value of texture analysis of the primary tumour in high-risk neuroblastoma: An 18 F-DOPA PET study.

PURPOSE: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). METHODS: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). RESULTS: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both. CONCLUSIONS: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.

Diagnostic and Prognostic Role of 18F-Fluoroestradiol PET in Metastatic Breast Cancer: The Second Youth of an Older Theranostic Concept.

Since the discovery of the role of female hormones in breast cancer (BC) pathophysiology, in vivo detection of oestrogen receptor (ER) distribution has been one of the major goals of nuclear medicine and molecular imaging [...].

Diagnostic Performance of 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) for Risk Stratification of Hypofunctioning Thyroid Nodules: A European Multicenter Study.

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: -19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

Head-to-Head Comparison between 18F-FES PET/CT and 18F-FDG PET/CT in Oestrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-Analysis.

18F-FDG PET/CT is a powerful diagnostic tool in breast cancer (BC). However, it might have a reduced sensitivity in differentiated, oestrogen receptor-positive (ER+) BC. In this setting, specific molecular imaging with fluorine-oestradiol (18F-FES) PET/CT could help in overcoming these limitations; however, the literature on the diagnostic accuracy of this method is limited. We therefore planned this systematic review and meta-analysis to compare 18F-FDG and 18F-FES PET/CT in ER+ BC patients. We performed a literature search to identify all studies performing a head-to-head comparison between the two methods; we excluded review articles, preclinical studies, case reports and small case series. Finally, seven studies were identified (overall: 171 patients; range: 7-49 patients). A patients-based analysis (PBA) showed that 18F-FDG and 18F-FES PET/CT had a similar high pooled sensitivity (97% and 94%, respectively) at the lesion-based analysis (LBA), 18F-FES performed slightly better than 18F-FDG (pooled sensitivity: 95% vs. 85%, respectively). Moreover, when we considered only the studies dealing with the restaging setting (n = 3), this difference in sensitivity was even more marked (98% vs. 81%, respectively). In conclusion, both tracers feature an excellent sensitivity in ER+ BC; however, 18F-FES PET/CT could be preferred in the restaging setting.

Role of Dynamic Parameters of 18F-DOPA PET/CT in Pediatric Gliomas.

PURPOSE OF THE REPORT: PET with 18F-DOPA can be used to evaluate grading and aggressiveness of pediatric cerebral gliomas. However, standard uptake parameters may underperform in circumscribed lesions and in diffuse pontine gliomas. In this study, we tested whether dynamic 18F-DOPA PET could overcome these limitations. PATIENTS AND METHODS: Patients with available dynamic 18F-DOPA PET were included retrospectively. Static parameters (tumor/striatum ratio [T/S] and tumor/cortex ratio [T/N]) and dynamic ones, calculated on the tumor time activity curve (TAC), including time-to-peak (TTP), slope steepness, the ratio between tumor and striatum TAC steepness (dynamic slope ratio [DSR]), and TAC shape (accumulation vs plateau), were evaluated as predictors of high/low grading (HG and LG) and of progression-free survival and overall survival. RESULTS: Fifteen patients were included; T/S, T/N, TTP, TAC slope steepness, and DSR were not significantly different between HG and LG. The accumulation TAC shape was more prevalent in the LG than in the HG group (75% vs 27%). On progression-free survival univariate analysis, TAC accumulation shape predicted longer survival (P < 0.001), whereas T/N and DSR showed borderline significance; on multivariate analyses, only TAC shape was retained (P < 0.01, Harrell C index, 0.93-0.95). On overall survival univariate analysis, T/N (P < 0.05), DSR (P < 0.05), and TAC "accumulating" shape predicted survival (P < 0.001); once more, only this last parameter was retained in the multivariate models (P < 0.05, Harrell C index, 0.86-0.89). CONCLUSIONS: Dynamic 18F-DOPA PET analysis outperforms the static parameter evaluation in grading assessment and survival prediction. Evaluation of the curve shape is a simple-to-use parameter with strong predictive power.

Radiomics analysis improves 18FDG PET/CT-based risk stratification of cytologically indeterminate thyroid nodules.

PURPOSE: As ~25% of cytologically indeterminate thyroid nodules harbour malignancy, diagnostic lobectomy is still performed in many cases. 18FDG PET/CT rules out malignancy in visually negative nodules; however, none of the currently available interpretation criteria differentiates malignant from benign 18FDG-avid nodules. We evaluated the ability of PET metrics and radiomics features (RFs) to predict final diagnosis of 18FDG-avid cytologically indeterminate thyroid nodules. METHODS: Seventy-eight patients were retrospectively included. After volumetric segmentation of each thyroid lesion, 4 PET metrics and 107 RFs were extracted. A logistic regression was performed including thyroid stimulating hormone, PET metrics, and RFs to assess their predictive performance. A linear combination of the resulting parameters generated a radiomics score (RS) that was matched with cytology classes (Bethesda III and IV) and compared with final diagnosis. RESULTS: Two RFs (shape_Sphericity and glcm_Autocorrelation) differentiated malignant from benign lesions. A predictive model integrating RS and cytology classes effectively stratified the risk of malignancy. The prevalence of thyroid cancer increased from 5 to 37% and 79% in accordance with the number (score 0, 1 or 2, respectively) of positive biomarkers. CONCLUSIONS: Our multiparametric model may be useful for reducing the number of diagnostic lobectomies with advantages in terms of costs and quality of life for patients.