Background Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial. Methods We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models. Results Of 8475 women (mean age at diagnosis: 45 years, range 2–90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36–1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84–1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI −4 to 13) and 42 (95% CI −8 to 93) excess breast cancer cases per 10,000 person-years, respectively. Conclusions An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors.

Purpose To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([ 18 F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. Methods This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January–February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. Results Overall, [ 18 F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) ( p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). Conclusions A significant increase of interstitial pneumonia incidentally detected with [ 18 F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (2-[18F]FDG-PET) has an emerging supportive role in dementia diagnostic as distinctive metabolic patterns are specific for Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Previous studies have demonstrated that a data-driven decision model based on the disease state index (DSI) classifier supports clinicians in the differential diagnosis of dementia by using different combinations of diagnostic tests and biomarkers. Until now, this model has not included 2-[18F]FDG-PET data. The objective of the study was to evaluate 2-[18F]FDG-PET biomarkers combined with commonly used diagnostic tests in the differential diagnosis of dementia using the DSI classifier. We included data from 259 subjects diagnosed with AD, DLB, FTD, vascular dementia (VaD), and subjective cognitive decline from two independent study cohorts. We also evaluated three 2-[18F]FDG-PET biomarkers (anterior vs. posterior index (API-PET), occipital vs. temporal index, and cingulate island sign) to improve the classification accuracy for both FTD and DLB. We found that the addition of 2-[18F]FDG-PET biomarkers to cognitive tests, CSF and MRI biomarkers considerably improved the classification accuracy for all pairwise comparisons of DLB (balanced accuracies: DLB vs. AD from 64% to 77%; DLB vs. FTD from 71% to 92%; and DLB vs. VaD from 71% to 84%). The two 2-[18F]FDG-PET biomarkers, API-PET and occipital vs. temporal index, improved the accuracy for FTD and DLB, especially as compared to AD. Moreover, different combinations of diagnostic tests were valuable to differentiate specific subtypes of dementia. In conclusion, this study demonstrated that the addition of 2-[18F]FDG-PET to commonly used diagnostic tests provided complementary information that may help clinicians in diagnosing patients, particularly for differentiating between patients with FTD, DLB, and AD.

To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. EudraCT no.: 2014-005389-31

Background:In Alzheimer's disease (AD) diagnosis, both cerebrospinal fluid (CSF) biomarkers and FDG-PET sometimes give inconclusive results. Objective:To evaluate the incremental diagnostic value of FDG-PET over CSF biomarkers, and vice versa, in patients with mild cognitive impairment (MCI) and su spected AD, in which the first biomarker resulted inconclusive. Methods:A consecutive series of MCI patients was retrospectively selected from two Memory Clinics where, as per clinical routine, either the first biomarker choice is FDG-PET and CSF biomarkers are only used in patients with uninformative FDG-PET, or vice versa. We defined criteria of uncertainty in interpretation of FDG-PET and CSF biomarkers, according to current evidence. The final diagnosis was established according to clinical-neuropsychological follow-up of at least one year (mean 4.4±2.2). Results:When CSF was used as second biomarker after FDG-PET, 14 out of 36 (39%) received informative results. Among these 14 patients, 11 (79%) were correctly classified with respect to final diagnosis, thus with a relative incremental value of CSF over FDG-PET of 30.6%. When FDG-PET was used as second biomarker, 26 out of 39 (67%) received informative results. Among these 26 patients, 15 (58%) were correctly classified by FDG-PET with respect to final diagnosis, thus with a relative incremental value over CSF of 38.5%. Conclusion:Our real-world data confirm the added values of FDG-PET (or CSF) in a diagnostic pathway where CSF (or FDG-PET) was used as first biomarkers in suspected AD. These findings should be replicated in larger studies with prospective enrolment according to a Phase III design.

BACKGROUND:Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET.OBJECTIVE:We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls.METHODS:Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [18]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM).RESULTS:The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods.CONCLUSION:The study confirms the good accuracy of [18]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.

Amyloid PET and CSF Aβ42 have demonstrated analytical and clinical validity, but their comparative clinical utility is unclear. The aim of this study is to compare the incremental diagnostic value of [18F]-Florbetaben PET and CSF markers (Aβ42, tau and ph-tau) in patients with cognitive impairment. 75 patients satisfying AUC for amyloid PET underwent dementia workup for suspected primary dementia, including amyloid PET and CSF markers, and routine diagnosis and treatment. Clinical, imaging, and biomarker features were recorded. Two experienced dementia specialists (FA and AM), blind to the local physician's diagnosis, made an etiological diagnosis in 3 rounds based on patients’ files. In round 1, they were asked to provide the etiologic diagnosis and diagnostic confidence based on clinical information, neuropsychological tests and structural MRI scans. In round 2, they were fed with the result of CSF for half of the patients, and PET for the other half, and asked to update diagnosis and diagnostic confidence. In round 3, they were fed with the other biomarker and again asked a diagnostic update. ±7 years; 73.7% had a suspected diagnosis of AD and 26.3% of non-AD after round 1; 59.6% were amyloid PET and 47.4% CSF Aβ42 negative. In suspected AD amyloid negative patients, diagnostic change occurred in 60% after CSF Aβ42 and 100% after amyloid PET at round 1 (P=0.026), and in 0% after CSF and 88% after amyloid PET at round 2 (P<0.001). In suspected non-AD, diagnostic change was not statistically in this preliminary analysis. Amyloid-PET led to a higher increase of diagnostic confidence than CSF both at round 1 (+6%, P=0.030) and at round 2 (+5%, P=0.009). In patients with suspected primary dementia and satisfying AUC for amyloid PET, the latter demonstrated a greater impact than CSF Aβ42on diagnosis and diagnostic confidence, both when used as a first-line and as a second-line biomarker after CSF. The results of the INDIA-FBB study can be useful to cost-benefit ratio assessments.

A 68-year-old lawyer developed insidious disturbances in topographic orientation and apraxia. He underwent a geriatric evaluation, only documenting slight cognitive disturbances, and a 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), showing mild right-lateralised frontoparietal hypometabolism. After 1 year, because of worsening in spatial orientation and the onset of dressing apraxia, he was referred to our memory clinic. The neuropsychological evaluation documented proeminent visuospatial, praxis deficits and dysgraphia. Cerebrospinal fluid biomarker analysis showed mild increase of total-τ, with normal Aβ1-42, ruling out Alzheimer's disease. Progression of the right parietal hypometabolism at FDG-PET and right superior longitudinal fasciculus damage at high-field MRI revealed a probable neurodegenerative aetiology. The neurological examination disclosed then Gerstmann's and Balint's syndromes, and extrapyramidal signs later appeared, suggesting the diagnosis of posterior cortical atrophy associated with corticobasal syndrome. Genetic analysis for mutations inmicrotubule-associated protein tau (MAPT), C9orf72 and GRN genes was negative. A 1-year follow-up documented significant worsening of the cognitive and functional impairment, revealing a frank dementia.

The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11–87) with differentiated thyroid carcinoma (DTC).

CSF biomarkers and amyloid PET imaging are pathophysiological, ie diagnostic, markers of Alzheimer's Disease (AD). The reduction of CSF Aβ42 levels precedes the positivity of amyloid PET imaging (Mattsson et al., 2015; Palmqvist et al., 2016), where the latter may represent a more advanced stage of the disease compared to the earlier positivity of CSF biomarkers. Correlation studies between amyloid PET and CSF biomarkers show that CSF Aβ42/t-tau and Aβ42/p-tau ratios have similar diagnostic accuracies as the best amyloid PET measures, performing better than Aβ42/40 ratio (Palmqvist et al., 2015). In this study we assessed the correlations of CSF biomarkers, expressed as different ratios (Aβ42/Aβ40, Aβ42/t-Tau, Aβ42/p-Tau), with amyloid PET positivity. The aim was to check if also tau proteins, a marker of neurodegeneration downstream to amyloidosis, are associated with amyloid PET imaging positivity. Patients showing different severity of cognitive impairment (from pre-MCI to mild dementia) underwent lumbar puncture and amyloid PET for diagnostic purposes. CSF Aβ42, Aβ40, t-tau and p-tau were measured using commercially available ELISA kits (INNOTEST, Fujirebio Europe, Gent, Belgium). Cerebral Aβ deposition was detected with the 18F-labelled tracer florbetaben (NeuraCeqTM) and assessed with a regional cortical tracer uptake scoring system (Villemagne et al., 2011; Barthel et al., 2011). The resulting scores were condensed into an overall Brain Amyloid Pathology Load (BAPL) score (score 1= negative; score 2 and 3= positive). Thirty-eight subjects (mean age 68.4 ± 5.4 yr, 12M/26F) have been assessed. Amyloid PET was positive in 13 (34.2%) subjects. At the cut-off of 19.9, Aβ42/p-Tau ratio provided the best performance, with 100% sensitivity and 88% specificity, in detecting a positive BAPL (AUC = 0.93, 95% CI = 0.82 to 1.00). The performance of Aβ42/t-Tau ratio was comparable (AUC = 0.91, 95% CI = 0.79 to 1.00). Ratios between Aβ42 and Tau species are highly associated with amyloid PET positivity. These findings may be explained by the different dynamic changes of CSF biomarkers, where Aβ species undergo a “plateau”, while tau species increase along the course of the disease. Amyloid PET detects the deposition of fibrillary amyloid, a relatively “late” phenomenon in AD pathogenesis.

Poster: EANM 17 / E-PW036 / Atlas-based pulmonary lobes segmentation implemented with MIM® for quantitative lung perfusion SPECT/CT analysis by: P. Fulcheri1, C. Tranfaglia2, V. Reggioli1, A. Chiappiniello3, R. Tarducci1, M. E. Dottorini2; 1Medical Physics Department, Hospital Santa Maria della Misericordia, Perugia, ITALY, 2Nuclear Medicine Department, Hospital Santa Maria della Misericordia, Perugia, ITALY, 3Physics and Geology Department, University of Perugia, Perugia, ITALY

OBJECTIVE:The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT is an automatic classifier composed of a set of logical rules, organized as a decision tree to produce an optimised threshold based classification of data to provide discriminative cut-off values. We applied a CIT to 123I-FP-CIT brain SPET semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake ratios in caudate nuclei and putamina with the aim to diagnose PD versus other conditions.SUBJECTS AND METHOD:We retrospectively investigated 187 patients undergoing 123I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative analysis performed with Basal Ganglia (BasGan) V2 software according to EANM guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by other non parkinsonian conditions, such as Essential Tremor and drug-induced PD. PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6-38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All subjects were clinically followed for at least 6-18 months to confirm the diagnosis. To examinate data obtained by using CIT, for each of the 1,000 experiments carried out, 10% of patients were randomly selected as the CIT training set, while the remaining 90% validated the trained CIT, and the percentage of the validation data correctly classified in the two groups of patients was computed. The expected performance of an "average performance CIT" was evaluated.RESULTS:For CIT, the probability of correct classification in patients with PD was 84.19±11.67% (mean±SD) and in N patients 93.48±6.95%. For CIT, the first decision rule provided a value for the right putamen of 2.32±0.16. This means that patients with right putamen values <2.32 were classified as having PD. Patients with putamen values ≥2.32 underwent further analysis. They were classified as N if the right putamen uptake value was ≥3.02 or if the value for the right putamen was <3.02 and the age was ≥67.5 years. Otherwise the patients were classified as having PD. Other similar rules on the values of both caudate nuclei and left putamen could be used to refine the classification, but in our data analysis of these data did not significantly contribute to the differential diagnosis. This could be due to an increased number of more severe patients with initial prevalence of left clinical symptoms having a worsening in right putamen uptake distribution.CONCLUSION:These results show that CIT was able to accurately classify PD and non-PD patients by means of 123I-FP-CIT brain SPET data and provided also cut-off values able to differentially diagnose these groups of patients. Right putamen uptake values resulted as the most discriminant to correctly classify our patients, probably due to a certain number of subjects with initial prevalence of left clinical symptoms. Finally, the selective evaluation of the group of subjects having putamen values ≥2.32 disclosed that age was a further important feature to classify patients for certain right putamen values.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PURPOSE:The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain(18)F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance.METHODS:The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score.RESULTS:Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus.CONCLUSION:These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities.

Radioiodine is a safe and well-established therapeutic modality for the ablation of thyroid remnants and the treatment of locoregional and distant metastases from differentiated thyroid carcinoma. However, a careful hazard assessment is mandatory in order to establish the risk–benefit ratio, especially in low-risk patients. Induction of second primary malignancies is one of the most serious possible untoward effects of radioiodine treatment. The limited incidence both of this effect and of thyroid cancer and the paucity of available dosimetric data make it difficult to perform high-quality studies that could provide evidence-based indications. A number of bias and confounding factors can blur data and must be considered, evaluating studies, addressing this topic. Data from the main surveys confirm that radioiodine can induce second primary tumors, with a probability comparable to that of external radiotherapy and lower than that of chemotherapy. Even though radioiodine treatment of thyroid cancer carries a low relative risk, the process of therapy justification must be carefully conducted and every measure that can reduce patient exposure must be taken, especially in children, adolescents and young adults.