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Background: Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of various molecular targets that can be used for diagnostic nuclear medicine imaging and radiopharmaceutical treatment. Theragnostics is based on the binding of radionuclides to molecular targets. These radionuclides can induce a cytotoxic effect on the specific tumor cell (target) or its vicinity, thus allowing a personalized approach to patients with effective treatment and comparably small side effects. Aim: This review aims to describe the most promising molecular targets currently under investigation for theragnostics and precision oncology in breast cancer. Methods: A comprehensive literature search of studies on theragnostics in breast cancer was performed in the PubMed, PMC, Scopus, Google Scholar, Embase, Web of Science, and Cochrane library databases, between 2010 and 2022, using the following terms: breast neoplasm*, breast, breast cancer*, theragnostic*, theranostic*, radioligand therap*, RLT, MET, FLT, FMISO, FES, estradiol, trastuzumab, PD-L1, PSMA, FAPI, FACBC, fluciclovine, FAZA, GRPR, DOTATOC, DOTATATE, CXC4, endoglin, gastrin, mucin1, and syndecan1. Results: Fifty-three studies were included in the systematic review and summarized in six clinical sections: 1) human epidermal growth factor receptor 2 (HER2); 2) somatostatin receptors (SSTRS); 3) prostate-specific membrane antigen radiotracers (PSMA); 4) fibroblast activation protein-α targeted radiotracers; 5) gastrin-releasing peptide receptor-targeted radiotracers; 6) other radiotracers for theragnostics. Conclusion: The theragnostic approach will progressively allow better patient selection, and improve the prediction of response and toxicity, avoiding unnecessary and costly treatment.

Introduction: this retrospective study aims to establish 18F-fluorocholine (FCH) positron emission tomography / computed tomography (PET/CT) performance in finding hyperfunctioning parathyroid glands, analyse a potential role for semi-quantitative PET parameters and assess factors that may influence PET/CT outcome.Methods: forty patients with suspect primary hyperparathyroidism (pHPT) and negative/equivocal conventional imaging underwent FCH-PET/CT in our Institution.For every lesion, visual and semi-quantitative analyses were performed on PET/CT images. In qualitative analysis, a lesion was considered positive if a clear focus of uptake, significantly higher than normal thyroid tissue, was identifiable. Ectopic focal uptake was also regarded as positive PET result. Lesion SUVMax was measured by assigning a spheric VOI to the suspect area of uptake. Thyroid SUVMean was assessed by placing a spheric VOI inside the contralateral thyroid lobe, and SUVratio was calculated using this background region.All patients were subsequently submitted to surgery and histopathologic workup.Sensitivity, positive predictive value (PPV) and accuracy were calculated based on histopathologic reports for every lesion.Pearson’s test was used to assess a correlation between laboratory and histopathologic features with SUVr.Results: four out of the 40 patients who underwent surgery for pHPT had more than one histologic proven unhealthy parathyroid and three had papillary thyroid cancer (PTC). A total of 48 lesions were analysed.We found 42/48 lesions (87.5%) to have true-positive uptake, whereas three lesions (6.7%) had false-positive uptake (PTC). Three histologic proven parathyroid adenomas showed no uptake (6.7%); the sensitivity/PPV were 93.3% and accuracy was 87,8%.Pearson’s test showed a significant correlation between PTH values and parathyroid size with SUVr values (r=0.56 and 0.55 respectively, pDiscussion: as stated in recent literature, we observed excellent diagnostic sensitivity of FCH-PET/CT in patients with pHPT, providing surgeons a fine tool to optimize treatment.More studies are needed to improve the evaluability of semi-quantitative parameters towards a further improvement of diagnostic accuracy.

AIM: to examine the role of FDG PET/CT for assessing response to immunotherapy in patients with solid tumors. MATERIALS AND METHODS: data recorded in a multicenter (n=17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET images, and the two were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (n=177, 56.9%), followed by malignant melanoma (n=101, 32.5%). Nivolumab was administered in 144 of the former patients (46.3%), and pembrolizumab in 126 of the latter (40.5%). Baseline PET and a first PET scan performed a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. At successive time points, the consistency between PET scans and clinical findings was 37%, 54%, 26%, 37%, and 29%, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on two or more PET scans after starting immunotherapy had a better prognosis than non-responders (all pCONCLUSIONS: FDG PET/CT should have a role in the assessment of response to immunotherapy in patients with solid tumors. It can provide prognostic information and thus contribute to a patient’s appropriate treatment.

The present review aims to discuss indications for the use of [18F]-FDG PET in patients with APS associated with dementia as emerged in the EANM/EAN joint recommendations for its use in dementia. New lines of evidence emerged after the EANM/EAN consensus have here been systematically reviewed. We searched in the databases PubMed, PMC, Google Scholar, Medline using as text “positron emission tomography—PET”, “PET/CT”, “MR” and “Parkinsonian Syndromes”, “Atypical Parkinsonism”, “progressive supranuclear palsy”, “cortico-basal syndrome”, “dementia with Lewy Bodies”. We selected only PET studies or multimodal imaging studies including the use of [18F]-FDG PET. Atypical parkinsonian syndromes (APS) associated with dementia are complex clinical scenarios including progressive supranuclear palsy (PSP), corticobasal syndrome/degeneration (CBS/CBD) and dementia with Lewy bodies (DLB). The clinical diagnosis of these diseases is often challenging and has relevant repercussions for patients’ management and prognosis. A systematic review of the articles published between December 2015 and December 2019 (so after the deadline of the literature search at the time of the EAN/EANM recommendations) was carried out. A total of further 18 papers met our inclusion criteria. Although available studies in patients with APS and dementia suffer from methodological limitations, the expert consensus emerged from the EANM/EAN recommendations was in favor of its use for specific clinical questions in these group of patients. Studies in a larger number of patients published after the publication of the joint recommendations have further supported the use of 18F-FDG PET in patients with APS associated with dementia.

Several studies have investigated sex differences in morphological and functional neuroimaging in healthy conditions, but few data are available on the specific effect of sex on neuroimaging in dementia and related disorders. Sex is more often considered as a confounding variable than as a variable of interest. Furthermore, especially in the dementia field, the data are drawn from studies designed for other specific aims, and discrepant results are often found due to different equipment, studied cohorts, and analytical methods. Notably, investigating this aspect would be pivotal to better understand how age-related diseases, such as dementia, differentially impact on the main correlates of brain functions in males and females. We review some of the main findings of the literature, highlighting the need for a more systematic appraisal of sex and even gender differences in future neuroimaging studies.

Background Amyotrophic Lateral Sclerosis (ALS) is characterized by a spectrum of phenotypes, but a few study addressed the presence of parkinsonian (PK) symptoms. Aim of our study was to investigate the occurrence of PK features in a prospective population-based cohort of ALS patients, determining their demographic, clinical, neuropsychological and genetic characteristics, and identifying their morphological and functional imaging correlates. Methods A consecutive series of ALS patients were enrolled and prospectively followed for two years. Patients were classified according to the presence (ALS-PK) or absence (ALS) of PK signs, and they underwent neuropsychological testing, genetic analysis for the main ALS and PD genes, brain MRI and 18F-FDG-PET. ALS-PK patients underwent 123I-ioflupane SPECT Results Out of 114 eligible patients, 101 (64 men; mean age at onset 65.1 years) were recruited. Thirty-one patients (30.7%) were classified as ALS-PK. Compared to ALS patients, ALS-PK patients were more frequently male, but did not differ for any other clinical, demographic or neuropsychological factor. 123I-ioflupane SPECT was normal in all but two ALS-PK patients. At 18F-FDG-PET, ALSPK patients showed a relative hypometabolism in left cerebellum and a relatively more preserved metabolism in right insula and frontal regions; MRI fractional anisotropy was reduced in the sagittal stratum and increased in the retrolenticular part of the internal capsule. Conclusions In our study about 30% of ALS patients showed PK signs. Neuroimaging data indicate that PK signs are due to the involvement of brain circuitries other than classical nigrostriatal ones, strengthening the hypothesis of ALS as complex multisystem disease.

AIMS The aims of this study were: (1) to cross-compare data from semiquantitative, software-assisted, and phantom-corrected evaluations of 123I-ioflupane [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane FP-CIT brain single-photon emission computed tomography (SPECT) acquired in three centers; (2) to assess the accuracy of semiquantitative evaluation; and (3) to identify the threshold with the best accuracy, sensitivity, and specificity in patients with suspected Parkinsonian Syndrome. MATERIAL AND METHODS Two-hundred-twenty patients, acquired in three centers, were included. All of them underwent 123I-FP-CIT brain SPECT. All examinations were analyzed with the freely available software, BasGan, and semiquantitative data were used to predict disease. Analysis was based on the values from the most deteriorated putamen and caudate, normalized for age, and corrected by anthropomorphic phantom data. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUC) were estimated. RESULTS Analysis showed high AUCs (.880, .866, .920, and .882 for each center and multicenter setting). Best thresholds were 1.53 and 1.56 for putamen and caudate, respectively. Thresholds of putamen data showed sensitivity and specificity of 86% and 89%, respectively, in the multicenter setting. Neither sensibility nor specificity showed significant differences among centers. CONCLUSION A unique, accurate threshold for all centers, with high sensitivity and specificity was identified. Semiquantitative assessment of 123I-FP-CIT brain SPECT among different centers resulted reliable, accurate, and potentially useful in clinical trials.

Primitive mediastinal B-cell lymphoma (PMBCL) is a relatively rare form of non-Hodgkin lymphoma (NHL), typically concerning the youngster, with an aggressive course and poor prognosis. The therapy generally consists of high dose chemotherapy followed by radiotherapy. PET-CT is used at staging, restaging after chemotherapy and after radiotherapy, or when relapse is suspected. Aim of the study was to compare different criteria in the evaluation of response to chemotherapy in this setting.Thirty-eight patients with PMBCL (15 M, 23 F, median age 33 yrs [range 18-79]), all treated with chemo-immunotherapy and radiotherapy, who had undergone baseline (b-PET) and end of chemotherapy (f-CHT-PET) 18F-FDG-PET-CT scans at our institution between July 2004 and September 2014 were retrospectively re-evaluated; the median follow-up was 42 months (range 4-109), at which 4/38 (11%) had died, 5/38 (13%) were in partial response (PR) and 29/38 (76%) were in complete response (CR). The primary endpoint was progression-free survival (PFS), while the secondary one was overall survival (OS), according to the Cheson criteria. SUV max of the mediastinal disease mass at staging, of the residual mass at CT after chemo-immunotherapy, SUV max of the liver and of the mediastinal blood pool (MBP) were calculated for all patients.In our population, we observed that: 1) visual criteria performs better when positivity-negativity threshold is set at point 3 of the 5-point scale (5-PS); 2) semiquantitative approach by use of Δ SUV max performs better when the threshold is set at 66% decrease: in fact, at Δ SUV max analysis with 66% decrease, 9 patients resulted positive at the test (Δ SUV max ≤66%), 29 negative (Δ SUV max66%).In our population Δ SUV max could be working well in these patients because the baseline values are very high and very homogeneous. Our data, though limited in numerosity of patients and events, suggests that in this particular setting the use of the 5-PS reporting system could not be the best tool available; on the other hand, Δ SUV max could prove to be reliable in the evaluation of response to chemotherapy.

Background Different amyotrophic lateral sclerosis (ALS) phenotypes have been recognised, marked by a varying involvement of spinal and bulbar upper and lower motor neurons. However, the differential characteristics of these phenotypes are still largely unknown. Objective To define the epidemiology and outcome of ALS phenotypes in a population based setting. Methods All ALS cases incident in two Italian regions were prospectively collected from 1995 to 2004 in an epidemiological register. Cases were classified according to established ALS phenotypes: classic, bulbar, flail arm, flail leg, pyramidal, respiratory, pure lower motor neuron (PLMN) and pure upper motor neuron (PUMN). Results ALS phenotype were determined in 1332 out of 1351 incident patients (98.6%). Classic and bulbar phenotypes had similar mean annual incidence rates. Gender specific incidence rates showed a male preponderance in respiratory, flail arm, classic and PLMN phenotypes; in all other phenotypes, men and women had similar incidence rates. Age at onset was significantly lower in pyramidal, PLMN and PUMN phenotypes and higher in the bulbar phenotype. The best outcomes were observed in PUMN, pyramidal, PLMN and flail arm phenotypes and the worst in respiratory and bulbar phenotypes. Conclusions Our epidemiological findings suggest that ALS phenotypes carry distinctive and easily distinguishable clinical and prognostic characteristics, strongly related to a complex interplay between gender and age. The categorisation of ALS patients according to more homogenous clinical groups is relevant in identifying biological markers for ALS and should be considered for the design of clinical trials.