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Biocompatible gold nanoparticles (AuNPs) are particularly interesting for photo-thermal therapy (PTT) of cancer treatment because of their ability to convert light into heating efficiently. Nevertheless, the random accumulation of AuNPs in tissues, mainly determined by their retention time in the bloodstream, is one of the main limiting factors for their use in PTT applications. For this reason, efficient targeting and monitoring of AuNPs in the selected tissues is of paramount importance. This manuscript reports on a new generation of 99mTc-labeled AuNPs coated with keratin (Ker-AuNPs) and their spatial localization investigated by nuclear imaging techniques on an animal-free model. The effective radiolabeling of Ker-AuNPs with 99mTc is achieved using the chelating agent diethylenetriaminepentaacetic acid (DTPA), resulting in the 99mTc-DTPA-Ker-AuNPs nanoconjugate. The 99mTc-DTPA-Ker-AuNPs display a radiochemical purity of 90.7% and excellent photo-thermal properties. In addition, the biocompatibility of the 99mTc-DTPA-Ker-AuNPs with healthy human embryonic kidney (HEK293T) cells is shown. A Lab-On-a-Chip (LoC) approach is used to localize and study the stability of 99mTc-DTPA-Ker-AuNPs under dynamic conditions. To this end, the nanoconjugates are injected into a polydimethylsiloxane microfluidic chip mimicking the renal filtering unit, the nephron, and monitored via radio-imaging and thermo-optical experiments. These detailed studies establish that DTPA-assisted 99mTc-labeled Ker-AuNPs are excellent candidates as biocompatible and non-invasive radiolabeled nanotherapeutic for PTT-based applications.

Background: 123 I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123 I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts., Results: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123 I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I., Conclusions: The relationship between cardiac 123 I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs., (© 2024. The Author(s).)

Aims: Recovery of cardiovascular diagnostic testing in Italy after the coronavirus disease-2019 (COVID-19) pandemic has not been quantified. The study aims to describe cardiac diagnostic procedure volumes, centres practice and protocols, and staff members' well-being 1 year after COVID-19 outbreak in Italy., Methods and Results: A global survey was conducted by the International Atomic Energy Agency to evaluate changes in cardiac diagnostic procedure volumes in April 2021. Evaluated procedures were transoesophageal echocardiogram, coronary computed tomography angiography, coronary artery calcium scanning, nuclear medicine infection studies, invasive coronary angiography, rest and stress transthoracic echocardiogram, cardiac magnetic resonance, single-photon emission computed tomography and positron emission tomography, and stress electrocardiogram. Data were compared with April 2020 and March 2019. Forty-two Italian centres took part in the survey. In April 2020, there was a 72% decrease of median volumes of cardiac diagnostic procedures compared with March 2019. In April 2021, volumes of cardiac diagnostic procedures remained decreased by 3% when compared with March 2019. Stress electrocardiogram, coronary computed tomography angiography, and stress cardiac magnetic resonance volumes increased in April 2021 compared with baseline (29%, 6%, and 16%, respectively). The majority of centres had adopted physical distancing measures (93%), COVID-19 screening through questionnaires (76%), or temperature checks (93%). Twenty-five per cent of physicians at Italian responding sites reported excessive levels of psychological stress., Conclusion: In April 2021, volumes of cardiac diagnostic procedures at Italian responding sites were still recovering. Centres had implemented several adaptations to ensure the provision of care to their patients. Even 1 year after the pandemic, a substantial minority of Italian healthcare providers were still experiencing excessive psychological stress., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Menopause-related musculoskeletal (MSK) disorders include osteoporosis, osteoarthritis (OA), sarcopenia and sarco-obesity. This review focuses on the applications of nuclear medicine for the functional imaging of the aforementioned clinical conditions. Bone Scan (BS) with 99m Tc-labeled phosphonates, alone or in combination with MRI, can identify "fresh" vertebral collapse due to age-associated osteoporosis and provides quantitative parameters characterized by a good correlation with radiological indices in patients with OA. 18 F-NaF PET, particularly when performed by dynamic scan, has given encouraging results for measuring bone turnover in osteoporosis and allows the evaluation of subchondral bone metabolic activity in OA. FDG PET can help discriminate between pathological and nonpathological vertebral fractures, especially by applying appropriate SUV-based thresholds. In OA, it can effectively image inflamed joints and support appropriate clinical management. Preliminary evidences suggest a possible application of FDG in sarco-obesity for the detection and quantification of visceral adipose tissue (VAT). Further studies are needed to better define the role of nuclear medicine in menopause-related MSK disease, especially as regards the possible impact of new radiopharmaceuticals (ie, FAPI and RGD peptides) and recent technological advances (eg, total-body PET/CT scanners)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator receptor in oncology., Methods: A literature search was conducted in PubMed, Web of Science and Scopus databases up to June 2023. The results were presented according to the PRISMA guidelines. The quality of the studies was assessed using the Critical Appraisal Skill Program checklist., Results: Seven papers were selected for final analysis, involving 266 patients with solid tumors who underwent PET with uPAR-ligands. Thematic areas identified include feasibility studies ( n  = 2) on the safety, pharmacokinetics, and dosimetry of uPAR-targeting radiopharmaceuticals; uPAR-directed imaging in head and neck cancer ( n  = 2); uPAR PET in prostate cancer ( n  = 2); and the investigation of uPAR in neuroendocrine neoplasms ( n  = 1). Six of the seven studies used the radiopharmaceutical [ 68 Ga]Ga-NOTA-AE105 while one study used [ 64 Cu]Cu-DOTA-AE105. The studies showed protocol homogeneity, with static PET imaging at 20 minutes. The quality assessment revealed limitations such as small cohorts and the fact that all studies were performed by a single research group., Conclusions: uPAR-PET appears to be a promising imaging tool in well-selected oncological settings, but it needs to be validated by multicentre collaboration.

Purpose: Technetium-99m ( 99m Tc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration., Conclusion: The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed.

Background: Parkinson's disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8-18 per 100,000 people per year and 0.3-1%, respectively. As parkinsonian symptoms do not appear until approximately 50-60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson's disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients., Methods: 288 consecutive patients with suspected diagnoses of Parkinson's disease or non- Parkinson's disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other., Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson's disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy ( p < 0.001)., Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson's disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson's disease.

Background: Radio-guided surgery is a reliable approach used for localizing ground-glass opacities, lung nodules, and metastatic lymph nodes. Lung nodules, lymph node metastatic involvement, and ground-glass opacities often represent a challenge for surgical management and clinical work-up., Methods: PubMed research was conducted from January 1997 to June 2023 using the keywords "radioguided surgery and lung cancer"., Results: Different studies were conducted with different tracers: technetium-99m-albumin macroaggregates, cyanoacrylate combined to technetium-99m-sulfur colloid, indium-111-pentetreotide, and fluorine-18-deoxyglucose. A study proposed naphthalocyanine radio-labeled with copper-64. Radio-guided surgery has been demonstrated to be a reliable approach in localizing a lesion, and has a low radiological burden for personnel exposure and low morbidity. The lack of necessity to conduct radio-guided surgery under fluoroscopy or echography makes this radio-guided surgery an easy way of performing precise surgical procedures., Conclusions: Radio-guided surgery is a feasible approach useful for the intraoperative localization of ground-glass opacities, lung nodules, and metastatic lymph nodes. It is a valid alternative to the existing approaches due to its low cost, associated low morbidity, the possibility to perform the procedure after several hours, the low radiation dose applied, and the small amount of time that is required to perform it.

Background: Persistent dyspnea is frequent in post-COVID patients, even in the absence of pulmonary embolism (PE). In this scenario, the role of lung perfusion scintigraphy is unclear. The present study correlated scintigraphy-based semiquantitative perfusion parameters with chest high-resolution computed tomography (hrCT) volumetric indexes and clinical data in post-COVID patients with persistent dyspnea., Research Design and Methods: Sixty patients (30 post-COVID and 30 not previously affected by COVID-19) with persistent dyspnea submitted to lung perfusion scintigraphy and hrCT were retrospectively recruited. Perfusion rates of the pulmonary fields and hrCT-based normalized inflated, emphysematous, infiltrated, collapsed, and vascular lung volumes were calculated. Inflammatory and coagulation biomarkers were collected. PE at imaging was an exclusion criterion., Results: Compared to controls, reduced perfusion rates of the lower pulmonary fields and higher perfusion rates of the middle ones were observed in post-COVID patients, while hrCT findings were superimposable between the two groups. Perfusion rates of lower pulmonary fields were significantly associated only with abnormal lung volumes at hrCT., Conclusions: In post-COVID dyspnea without PE, lung perfusion scintigraphy may reveal a pulmonary involvement not detectable by hrCT. Post-COVID patients may show decreased perfusion rates of lower pulmonary fields in the presence of normal vascular density and markers of inflammation/coagulation.

Background: 123 I-mIBG-scintigraphy could be a useful stratifying tool for patients with heart failure (HF). The purpose of this retrospective study is to evaluate whether there are differences between men and women with HF in terms of the prediction of cardiac arrhythmic events (AE)., Research and Methods: A total of 306 patients, before implantable-cardioverter-defibrillator (ICD) implantation, were evaluated. They underwent 123 I-mIBG-scintigraphy and an evaluation of the results was performed after 85 months of follow-up. Early and late planar and SPECT cardiac images were acquired. Heart-to-mediastinum ratio (HM) for planar images and the sum of the segmental scores (SS) for SPECT were calculated., Results: In the general population, age, early SS (ESS), late SS (LSS), and ejection fraction (EF) were statistically significant for the prediction of AE at Cox regression, while early and late HM (eHM,lHM) were not significative for the prediction of AE. Population was divided into females and males and univariate analysis was conducted separately for the two cohorts: no significant variables for prediction of AE were found in females. For males, ESS, LSS, EF, and late HM were statistically significant predictors of AE. The overall survival was similar in males and females, but the risk of AE is lower in males than in females., Conclusions: 123 I-mIBG represents a more effective tool for the prediction of AE in male patients than in women.

Introduction: This review provides an update of 18 F-fluorodeoxyglucose ([ 18 F] FDG) for Brown adipose tissue (BAT) activity quantification, whose role is not completely understood., Areas Covered: We conducted an unstructured search of the literature for any studies employing the [ 18 F] FDG PET in BAT assessment. We explored BAT quantification both in healthy individuals and in different pathologies, after cold exposure and as a metabolic biomarker. The assessment of possible BAT modulators by using [ 18 F] FDG PET is shown. Further PET tracers and novel developments for BAT assessments are also described., Expert Opinion: Further PET tracers and imaging modalities are under investigation, but the [ 18F ] FDG PET is currently the method of choice for the evaluation of BAT and further multicentric trials are needed for a better understanding of the BAT physiopathology, also after cold stimuli. The modulation of BAT activity, assessed by [ 18 F] FDG PET imaging, seems a promising tool for the management of conditions such as obesity and type 2 diabetes. Moreover, an interesting possible correlation of BAT activation with prognostic [ 18 F] FDG PET indices in cancer patients should be assessed with further multicentric trials.

Introduction: A bone scan (BS) plays a pivotal role in many oncological and non-oncological conditions. The planar BS is characterized by high sensitivity but low specificity. With respect to planar imaging, the implementation of single-photon emission computed tomography (SPECT) has allowed increased image contrast and more accurate tracer localization., Areas Covered: Recent technological innovations in the field of BS are treated, with a particular focus on multi-field-of-view devices allowing to cover the entire scan length with a 3D acquisition (WB-SPECT/CT). In addition, the applications of cadmium zinc telluride/CzT detectors capable of converting gamma photons directly into electrical impulses (i.e. 'digital SPECT') are discussed., Expert Opinion: Initial clinical experiences indicate that WB-SPECT/CT is characterized by higher sensitivity, diagnostic accuracy, and increased confidence in image interpretation with respect to the 'old-fashioned' BS (planar images with or without a single field-of-view SPECT). Furthermore, CzT-based detectors, thanks to their superior sensitivity, might be helpful to implement fast acquisition protocols. Further studies are needed to better define the clinical impact of bone CzT WB-SPECT/CT on patients' management and outcome, as well as its cost-benefit ratio.

Introduction: To discuss the current evidence about radiolabeled-FAPI in patients affected by pancreatic cancer by underlying the advantages, disadvantages, and the future perspectives also in the theragnostic field., Areas Covered: A literature search up until February 2023 was performed in PubMed, EBSCO, and EMBASE databases. Clinical reports, conference abstracts, editorials, and letters-to-the-editor were excluded. The results were presented according to the PRISMA guidelines. The quality of studies was evaluated by using the Critical Appraisal Skill Program checklist., Expert Opinion: From the initial 139 studies, 21 papers were selected for the final analysis. Ten papers were related to FAPI-uptake in health/benign/malignant pancreas, eight studies were focalized on the utility of radiolabeled-FAPI for the identification of premalignant and malignant pancreatic lesions and only three papers were related to the the theragnostic approach. Only two papers enrolled exclusively patients with pancreatic cancer undergoing FAPI-PET. In total, 55 patients underwent FAPI-PET for the identification of the suspicious mass/primary tumor ( n  = 43) and recurrent disease ( n  = 12). In both the studies, FAPI-PET detected more lesions than 2-[ 18 F]FDG. Preliminary data about the FAPI-based theragnostic approach in patients with pancreatic cancer ( n  = 9 patients, totally) are now available. Radiolabeled-FAPI is a promising agent for the identification of pancreatic malignant lesions, but further prospective studies are still necessary.

Introduction: Poly-ADP-ribose-polymerase inhibitors (PARPi), which exploit the processes of so-called 'synthetic lethality,' have been successfully implemented in oncological practice. However, not all patients respond to PARPi, and there is an unmet need for noninvasive biomarkers suitable for patient selection and monitoring during PARPi therapy., Areas Covered: The first clinical applications of molecular imaging with positron emission tomography/computed tomography (PET/CT) with [18F]-FluorThanatrace ([18F]-FTT) and [18F]-PARPi, highly effective PARP-ligands, in patients with several malignancies (head and neck, ovarian, prostate, and breast cancer) are covered, with a particular focus on its potential for pre-treatment selection and follow-up., Expert Opinion: By a search made on the most common database, such as PubMed and Google Scholar in a period from January 2010 and 2023, first clinical evidence suggests that PET/CT with [18F]-FTT and [18F]-PARPi might represent a reliable tool for in vivo imaging and quantification of PARP-1 expression in ovarian, prostate, breast, head, and neck cancer, supporting their potential usefulness for patient selection before PARPi-therapies. In addition, a reduction in [18F]-FTT uptake has been registered after therapy initiation and seems to be correlated with patient outcome after PARPi-based regimens. Further studies are needed to better address the value of PARPI-radiolabeled PET imaging in these clinical settings, especially as it concerns technical features such as optimal scan modality (dynamic vs. static) and timing.

The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy., Materials and Methods: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were independently reviewed to evaluate study inclusion. Duplicate, out-of-topic, and review papers, or editorials, articles, and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302., Results: Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. The content of each study was different; indeed, seven papers investigated the potential ability of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreover, two evaluated the prediction of response, and four investigated the utility of radiomics to predict the response to immunotherapy. Finally, two papers investigated the prediction of adverse events due to immunotherapy., Conclusions: Radiomics is promising for the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overcome.

The aim of this systematic review is to provide a comprehensive overview of the existing literature, comparing 18 F-fluorodeoxyglucose (FDG) and 11 C-methionine (MET) for the imaging of multiple myeloma (MM) with positron emission computed tomography (PET/CT). Relevant studies published from 2013 up to March 2023 were selected by searching Scopus, PubMed, and Web of Science. Selected imaging studies were analyzed using a modified version of the critical Appraisal Skills Programme (CASP). Ten studies encompassing 335 patients were selected. On a patient-based analysis, MET sensitivity ranged between 75.6% and 100%, resulting higher than that measured for FDG (0-100%). MET outperformed FDG for the detection of focal lesions, diffuse bone marrow involvement and mixed patterns. PET-derived parameters resulted higher for MET than for FDG, with a strong correlation with clinical variables (e.g., monoclonal component and beta-2-microglobulin levels, bone marrow infiltration, etc.), although FDG maintained a prognostic impact on outcome prediction. When compared to other tracers or imaging modalities, MET showed stronger correlation and inter-observer agreement than FDG. Although biased by the small cohorts and requiring confirmation through multicenter studies, preliminary findings suggest that MET-PET should be preferred to FDG for PET imaging of MM, or alternatively used as a complementary imaging modality. Some issues, such as tracer availability and the role of MET with respect to other emerging tracers (i.e., 68 Ga-pentixafor, 18 F-FACBC and 18 F-FET), should be the topic of further investigations.

Coronary artery disease (CAD) is the leading cause of death followed by cancer, in men and women. With risk factors being endemic and the increasing costs of healthcare for management and treatment, myocardial perfusion imaging (MPI) finds a central role in risk stratification and prognosis for CAD patients, but it comes with its limitations in that the referring clinician and managing team must be aware of and use at their advantage. This narrative review examines the utility of myocardial perfusion scans in the diagnosis and management of patients with ECG alterations such as atrioventricular block (AVB), and medications including calcium channel blockers (CCB), beta blockers (BB), and nitroglycerin which may impact the interpretation of the exam. The review analyzes the current evidence and provides insights into the limitations, delving into the reasons behind some of the contraindications to MPI.

Our aim was to provide a comprehensive overview of the existing literature concerning the clinical applications of positron emission computed tomography (PET) with radiopharmaceuticals targeting the translocator protein (TSPO) in gliomas. A literature search for studies about TSPO PET in the last 10 years (from 2013 to February 2023) was carried out on PubMed, Scopus, and Web of Science using the following keywords: "PET" AND "Gliomas" AND "TSPO". The Critical Appraisal Skills Program checklist for diagnostic test studies was used for testing the quality of selected papers. Ten articles were selected, encompassing 314 glioma patients submitted to PET/CT (9/10) or PET/MRI (1/10) with TSPO ligands. Among the various available TSPO tracers, the most frequently used was the third-generation ligand, [ 18 F]-GE-180. TSPO PET results were useful to identify anaplastic transformation in gliomas and for the prognostic stratification of patients bearing homogeneous genetic alterations. When compared to amino-acid PET, TSPO PET with [ 18 F]-GE-180 presented superior image quality and provided larger and only partially overlapping PET-based volumes. Although biased by some issues (i.e., small sample size, most of the studies coming from the same country), preliminary applications of TSPO PET were encouraging. Further studies are needed to define implications in clinical practice and shape the role of TSPO PET for patients' selection for potential TSPO-targeted molecular therapies.

(1) Background: Tauopathies are a group of diseases characterized by the deposition of abnormal tau protein. They are distinguished into 3R, 4R, and 3R/4R tauopathies and also include Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Positron emission tomography (PET) imaging represents a pivotal instrument to guide clinicians. This systematic review aims to summarize the current and novel PET tracers. (2) Methods: Literature research was conducted on Pubmed, Scopus, Medline, Central, and the Web of Science using the query "pet ligands" and "tauopathies". Articles published from January 2018 to 9 February, 2023, were searched. Only studies on the development of novel PET radiotracers for imaging in tauopathies or comparative studies between existing PET tracers were included. (3) Results: A total of 126 articles were found, as follows: 96 were identified from PubMed, 27 from Scopus, one on Central, two on Medline, and zero on the Web of Science. Twenty-four duplicated works were excluded, and 63 articles did not satisfy the inclusion criteria. The remaining 40 articles were included for quality assessment. (4) Conclusions: PET imaging represents a valid instrument capable of helping clinicians in diagnosis, but it is not always perfect in differential diagnosis, even if further investigations on humans for novel promising ligands are needed.

Purpose: To assess the diagnostic performance of Whole Body (WB)-MRI in comparison with 18F-Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) in lymphoma staging and to assess whether quantitative metabolic parameters from 18F-FDG-PET/CT and Apparent Diffusion Coefficient (ADC) values are related., Materials and Methods: We prospectively enrolled patients with a histologically proven primary nodal lymphoma to  undergo 18F-FDG-PET/CT and WB-MRI, both performed within 15 days one from the other, either before starting treatment (baseline) or during treatment (interim). Positive and negative predictive values of WB-MRI for the identification of nodal and extra-nodal disease were measured. The agreement between WB-MRI and 18F-FDG-PET/CT for the identification of lesions and staging was assessed through Cohen's coefficient k and observed agreement. Quantitative parameters of nodal lesions derived from 18F-FDG-PET/CT and WB-MRI (ADC) were measured and the Pearson or Spearman correlation coefficient was used to assess the correlation between them. The specified level of significance was p ≤ 0.05., Results: Among the 91 identified patients, 8 refused to participate and 22 met exclusion criteria, thus images from 61 patients (37 men, mean age 30.7 years) were evaluated. The agreement between 18F-FDG-PET/CT and WB-MRI for the identification of nodal and extra-nodal lesions was 0.95 (95% CI 0.92 to 0.98) and 1.00 (95% CI NA), respectively; for staging it was 1.00 (95% CI NA). A strong negative correlation was found between ADCmean and SUVmean of nodal lesions in patients evaluated at baseline (Spearman coefficient r s  = - 0.61, p = 0.001)., Conclusion: WB-MRI has a good diagnostic performance for staging of patients with lymphoma in comparison with 18F-FDG-PET/CT and is a promising technique for the quantitative assessment of disease burden in these patients., (© 2023. The Author(s).)

Introduction: Lung cancer (LC) is a leading cause of death among men and women, with non-small cell LC (NSCLC) accounting for a substantial portion of the histopathological spectrum and epidermal growth factor receptor (EGFR) mutations being correlated with its manifestation and evolution. Positron emission tomography (PET)/computed tomography has been the most widely used instrument to assess and monitor LC in a noninvasive way, including EGFR-mutated NSCLC, and its course during therapy, indicating to the referring physician the response to ongoing treatment or the lack of it. This systematic review aims to evaluate the feasibility and safety of radiolabeled EGFR tyrosine kinase inhibitors (TKis) in PET in clinical practice. Materials and Methods: From 1999 to April 2022 a Medline search was conducted on four different databases such as PubMed, Cochrane Library, Scopus, and Web of Sciences. Clinical studies were assessed by Quality Assessment of Diagnostic accuracy Studies-2 (QUADAS-2) and preclinical studies were also reported in this review. Results: Nine clinical studies were QUADAS-2 assessed and risk-of-bias assessment, and it turned out acceptable as two out of eight studies had low risk of bias in all four domains for risk-of-bias assessment, and the other four studies had three low-risk domains. The overall assessment for applicability risks was low. Conclusions: Radiolabeled EGFR-TKis in PET are a valid tool in identifying patients who may benefit from TKi therapy and who may not as a means to start an effective treatment. Although the number of clinical studies conducted so far is meager, these new PET tracers are already proving to be very useful in clinical settings as patient prognosis can be better assessed.

Background: Abscopal effect (AE) describes the ability of radiotherapy (RT) to induce immune-mediated responses in nonirradiated distant metastasis. Bone represents the third most frequent site of metastasis and an immunologically favorable environment for the proliferation of cancer cells. We revised the literature, searching documented cases of AE involving bone metastases (BMs) and evaluated the incidence of AE involving BMs in patients requiring palliative RT on BMs or non-BMs treated at our department., Methods: Articles published in the PubMed/MEDLINE database were selected using the following search criteria: ((abscopal effect)) AND ((metastases)). Patients with BMs, who underwent performed bone scintigraphy before and at least 2-3 months after RT, were selected and screened between January 2015 and July 2022. AE was defined as an objective response according to the scan bone index for at least one nonirradiated metastasis at a distance > 10 cm from the irradiated lesion. The primary endpoint was the rate of AE on BMs., Results: Ten cases experiencing AE of BMs were identified from the literature and eight among our patients., Conclusions: The analysis performed here suggests the use of hypofractionated radiotherapy as the only triggering factor for AE of BMs through the activation of the immune response.

Background: Insulinomas are the most common neuroendocrine neoplasms of the pancreas. Diagnosis is made through patient clinical presentation with hypoglycemia symptoms and imaging, such as EUS, CT, MRI, and functional imaging. Exendin-4 PET/CT (and SPECT/CT) is a new prominent radiotracer developed to image insulinomas. The aim of the study is to evaluate whether exendin-4 imaging is a useful tool in imaging for insulinoma patients when other imaging methods do not reach them., Methods: MEDLINE research conducted on PubMed, Scopus, and Web of Science gathered a total of 501 papers. Studies that evaluated exendin-4 SPECT and PET in insulinoma patients were screened and assessed through QUADAS-2 for risk of bias and applicability concerns' assessment. Sensitivity, specificity, and accuracy were reported when available., Results: A total of 13 studies were deemed eligible for a QUADAS 2 review. Studies included ranged from 2009 to 2022. The most-used tracer was 68 Ga-DOTA-exendin-4 in PET and 111 In-DTPA-exendin-4 in SPECT. Exendin-4 labeled with 99 mTc was also reported. The QUADAS-2 risk of bias assessment was overall low, with some unclear reports in the reference and index domains. Only two domains were at high risk of bias because of an explicated non-blind imaging review. Applicability concerns for bias were low in all domains. Reported sensitivities ranged from 95% to 100% and specificities from 20% to 100%., Conclusions: exendin-4 imaging is a sensitive functional imaging tracer in both SPECT and PET applications, especially in suspicion of benign insulinomas located where endoscopic ultrasound cannot reach, being more sensitive than morfostructural imaging.

Background/aim: Radium-223 dichloride ( 223 RaCl 2 ) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223 RaCl 2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223 RaCl 2 . For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units., Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis., Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223 RaCl 2 to the date of death from any cause or last contact was 13 months (95%CI 12-14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052-1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040-1.068, p < 0.001)., Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223 RaCl 2 . The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Background: Translocator protein (TSPO) is a neuroinflammation hallmark. Different TSPO affinity compounds have been produced and over time, the techniques of radiolabeling have been refined. The aim of this systematic review is to summarize the development of new radiotracers for dementia and neuroinflammation imaging., Methods: An online search of the literature was conducted in the PubMed, Scopus, Medline, Cochrane Library, and Web of Science databases, selecting published studies from January 2004 to December 2022. The accepted studies considered the synthesis of TSPO tracers for nuclear medicine imaging in dementia and neuroinflammation., Results: A total of 50 articles was identified. Twelve papers were selected from the included studies' bibliographies and 34 were excluded. Thus, 28 articles were ultimately selected for quality assessment., Conclusion: Huge efforts in developing specific and stable tracers for PET/SPECT imaging have been made. The long half-life of 18 F makes this isotope a preferable choice to 11 C. An emerging limitation to this however is that neuroinflammation involves all of the brain which inhibits the possibility of detecting a slight inflammation status change in patients. A partial solution to this is using the cerebellum as a reference region and developing higher TSPO affinity tracers. Moreover, it is necessary to consider the presence of distomers and racemic compounds interfering with pharmacological tracers' effects and increasing the noise ratio in images.

Parkinson's disease is the second most common neurodegenerative disorder, affecting 2-3% of the population of patients >65 years. Although the standard diagnosis of PD is clinical, neuroimaging plays a key role in the evaluation of patients who present symptoms related to neurodegenerative disorders. MRI, DAT-SPECT, and PET with [ 18 F]-FDG are routinely used in the diagnosis and focus on the investigation of morphological changes, nigrostriatal degeneration or shifts in glucose metabolism in patients with parkinsonian syndromes. The aim of this study is to review the current PET radiotracers targeting TSPO, a transmembrane protein that is overexpressed by microglia in another pathophysiological process associated with neurodegenerative disorders known as neuroinflammation. To the best of our knowledge, neuroinflammation is present not only in PD but in many other neurodegenerative disorders, including AD, DLB, and MSA, as well as atypical parkinsonian syndromes. Therefore, in this study, specific patterns of microglial activation in PD and the differences in distribution volumes of these radiotracers in patients with PD as compared to other neurodegenerative disorders are reviewed.

Background: Dendrimers are nanoscale-size polymers with a globular structure. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Different complexes have been developed for imaging and therapeutic purposes. This systematic review aims to summarize the development of newer dendrimers for oncological applications in nuclear medicine., Methods: An online literature search was conducted on Pubmed, Scopus, Medline, Cochrane Library, and Web Of Science databases selecting published studies from January 1999 to December 2022. The accepted studies considered the synthesis of dendrimer complexes for oncological nuclear medicine imaging and therapy., Results: 111 articles were identified; 69 articles were excluded because they did not satisfy the selection criteria. Thus, nine duplicate records were removed. The remaining 33 articles were included and selected for quality assessment., Conclusion: Nanomedicine has led researchers to create novel nanocarriers with high affinity for the target. Dendrimers represent feasible imaging probes and therapeutic agents since, through the functionalization of external chemical groups and thanks to the possibility to carry pharmaceuticals, it can be possible to exploit different therapeutic strategies and develop a useful weapon for oncological treatments.

Background: in recent years, the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) has emerged as a reliable diagnostic tool in a wide variety of pathological conditions. This review aims to collect and review PET criteria developed for interpretation and treatment response assessment in cases of non-[ 18 F]fluorodeoxyglucose ([ 18 F]FDG) imaging in oncology., Methods: A wide literature search of the PubMed/MEDLINE, Scopus and Google Scholar databases was made to find relevant published articles about non-[ 18 F]FDG PET response criteria., Results: The comprehensive computer literature search revealed 183 articles. On reviewing the titles and abstracts, 149 articles were excluded because the reported data were not within the field of interest. Finally, 34 articles were selected and retrieved in full-text versions., Conclusions: available criteria are a promising tool for the interpretation of non-FDG PET scans, but also to assess the response to therapy and therefore to predict the prognosis. However, oriented clinical trials are needed to clearly evaluate their impact on patient management.

Background: With the high mortality rate of malignant tumors, there is a need to find novel theranostic approaches to provide an early diagnosis and targeted therapy. The chemokine receptor 4 (CCR4) is highly expressed in various tumors and plays an important role in tumor pathogenesis. This systematic review aims to provide a complete overview on clinical and preclinical applications of the CCR4 receptor as a target for theranostics, using a systematic approach to classify and assemble published studies performed on humans and animals, sorted by field of application and specific tumor., Methods: A systematic literature search of articles suiting the inclusion criteria was conducted on Pubmed, Scopus, Central, and Web of Science databases, including papers published from January 2006 to November 2022. Eligible studies had to be performed on humans and/or in vivo/in vitro studying CCR4 expression in tumors. The methodological quality was assessed through the Critical Appraisal Skills Programme (CASP) assessing only the studies performed on humans., Results: A total of 17 articles were screened. The articles were assessed for eligibility with the exclusion of 4 articles. Ultimately, 13 articles were selected for the qualitative analysis, and six articles were selected for the critical appraisal skills program., Conclusions: The development of new radionuclides and radiopharmaceuticals targeting CCR4 show promising results in the theranostics of CCR4 sensible tumors. Although to widen its use in clinical practice, further translation of preclinical to clinical data is needed.

Cancer is the leading cause of death around the globe, followed by heart disease and stroke, with the highest mortality to this day. We have reached great levels of understanding of how these various types of cancer operate at a cellular level and this has brought us to what we call "precision medicine" where every diagnostic examination and the therapeutic procedure is tailored to the patient. FAPI is among the new tracers that can be used to assess and treat many types of cancer. The aim of this review was to gather all the known literature on FAPI theranostics. A MEDLINE search was conducted on four web libraries, PUBMED, Cochrane, Scopus, and Web of Sciences. All of the available articles that included both diagnoses and therapy with FAPI tracers were collected and put through the CASP (Critical Appraisal Skills Programme) questionnaire for systematic reviewing. A total of 8 records were deemed suitable for CASP review, ranging from 2018 to November 2022. These studies were put through the CASP diagnostic checklist, in order to assess the goal of the study, diagnostic and reference tests, results, descriptions of the patient sample, and future applications. Sample sizes were heterogeneous, both for size as well as for tumor type. Only one author studied a single type of cancer with FAPI tracers. Progression of disease was the most common outcome, and no relevant collateral effects were noted. Although FAPI theranostics is still in its infancy and lacks solid grounds to be brought into clinical practice, it does not show any collateral effects that prohibit administration to patients, thus far, and has good tolerability profiles.

This study aims to evaluate the reliability of qualitative and semiquantitative parameters of 18 F-FDG PET-CT, and eventually a correlation between them, in predicting the risk of malignancy in patients with solitary pulmonary nodules (SPNs) before the diagnosis of lung cancer. A total of 146 patients were retrospectively studied according to their pre-test probability of malignancy (all patients were intermediate risk), based on radiological features and risk factors, and qualitative and semiquantitative parameters, such as SUVmax, SUVmean, TLG, and MTV, which were obtained from the FDG PET-CT scan of such patients before diagnosis. It has been observed that visual analysis correlates well with the risk of malignancy in patients with SPN; indeed, only 20% of SPNs in which FDG uptake was low or absent were found to be malignant at the cytopathological examination, while 45.45% of SPNs in which FDG uptake was moderate and 90.24% in which FDG uptake was intense were found to be malignant. The same trend was observed evaluating semiquantitative parameters, since increasing values of SUVmax, SUVmean, TLG, and MTV were observed in patients whose cytopathological examination of SPN showed the presence of lung cancer. In particular, in patients whose SPN was neoplastic, we observed a median (MAD) SUVmax of 7.89 (±2.24), median (MAD) SUVmean of 3.76 (±2.59), median (MAD) TLG of 16.36 (±15.87), and a median (MAD) MTV of 3.39 (±2.86). In contrast, in patients whose SPN was non-neoplastic, the SUVmax was 2.24 (±1.73), SUVmean 1.67 (±1.15), TLG 1.63 (±2.33), and MTV 1.20 (±1.20). Optimal cut-offs were drawn for semiquantitative parameters considered predictors of malignancy. Nodule size correlated significantly with FDG uptake intensity and with SUVmax. Finally, age and nodule size proved significant predictors of malignancy. In conclusion, considering the pre-test probability of malignancy, qualitative and semiquantitative parameters can be considered reliable tools in patients with SPN, since cut-offs for SUVmax, SUVmean, TLG, and MTV showed good sensitivity and specificity in predicting malignancy.

The meeting and merging between innovative nanotechnological systems, such as nanoparticles, and the persistent need to outperform diagnostic-therapeutic approaches to fighting cancer are revolutionizing the medical research scenario, leading us into the world of nanomedicine. Photothermal therapy (PTT) is a non-invasive thermo-ablative treatment in which cellular hyperthermia is generated through the interaction of near-infrared light with light-to-heat converter entities, such as gold nanoparticles (GNPs). GNPs have great potential to improve recovery time, cure complexity, and time spent on the treatment of specific types of cancer. The development of gold nanostructures for photothermal efficacy and target selectivity ensures effective and deep tissue-penetrating PTT with fewer worries about adverse effects from nonspecific distributions. Regardless of the thriving research recorded in the last decade regarding the multiple biomedical applications of nanoparticles and, in particular, their conjugation with drugs, few works have been completed regarding the possibility of combining GNPs with the cancer-targeted pharmaceutical fluorodeoxyglucose (FDG). This review aims to provide an actual scenario on the application of functionalized GNP-mediated PTT for cancer ablation purposes, regarding the opportunity given by the 18 F-fluorodeoxyglucose ( 18 F-FDG) functionalization.

Background: Bone metastatic involvement represents a leading cause of death in patients with advanced breast cancer (BC). At present, it is not clear whether the bone metastatic load might impact Overall Survival (OS) in patients with bone metastatic BC at diagnosis. For this purpose, we used the Bone Scan Index (BSI), which is a reproducible and quantitative expression of tumor load observed at bone scintigraphy., Objective: The aim of this study was to associate BSI with OS in bone metastatic BC patients., Methods: In this retrospective study, we enrolled BC patients with bone metastases at the scintigraphic bone scan performed for staging purposes. The BSI was calculated through the DASciS software, and statistical analysis was carried out. Other clinical variables relevant to OS analysis were taken into account., Results: Of a total of 94 patients, 32% died. In most cases, the histotype was ductal infiltrating carcinoma. The median OS from diagnosis was 72 months (CI 95%: 62-NA). The univariate analysis with COX regression showed that only hormone therapy significantly correlates with OS (HR 0.417, CI 95%: 0.174-0.997, p < 0.049). As concerning BSI, the statistical analysis showed that it does not predict OS in BC patients (HR 0.960, 95% CI: 0.416-2.216, p < 0.924)., Conclusion: Although the BSI significantly predicts OS in prostate cancer and in other tumors, we observed that the metastatic load of bone disease has not a key role in prognostic stratification in our population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: In this research, our primary objective was to explore the correlation between basal ganglia dopaminergic neurotransmission, assessed using 123I-FP-CIT (DAT-SPECT), and finger movements abnormalities in patients with essential tremor (ET) and Parkinson's disease (PD)., Methods: We enrolled 16 patients with ET, 17 with PD, and 18 healthy controls (HC). Each participant underwent comprehensive clinical evaluations, kinematic assessments of finger tapping. ET and PD patients underwent DAT-SPECT imaging. The DAT-SPECT scans were subjected to both visual and semi-quantitative analysis using DaTQUANT®. We then investigated the correlations between the clinical, kinematic, and DAT-SPECT data, in patients., Results: Our findings confirm that individuals with ET exhibited slower finger tapping than HC. Visual evaluation of radiotracer uptake in both striata demonstrated normal levels within the ET patient cohort, while PD patients displayed reduced uptake. However, there was notable heterogeneity in the quantification of uptake within the striata among ET patients. Additionally, we found a correlation between the amount of radiotracer uptake in the striatum and movement velocity during finger tapping in patients. Specifically, lower radioligand uptake corresponded to decreased movement velocity (ET: coef. = 0.53, p-adj = 0.03; PD: coef. = 0.59, p-adj = 0.01)., Conclusion: The study's findings suggest a potential link between subtle changes in central dopaminergic tone and altered voluntary movement execution, in ET. These results provide further insights into the pathophysiology of ET. However, longitudinal studies are essential to determine whether the slight reduction in dopaminergic tone observed in ET patients represents a distinct subtype of the disease or could serve as a predictor for the clinical progression into PD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of the present review was to assess the impact of DNA damage repair (DDR) mutations on response and outcome of patients (pts) affected by advanced prostate cancer (PCa) submitted to radionuclide therapies with [223Ra]RaCl2 (223Ra-therapy) or prostate specific membrane antigen (PSMA) ligands. A systematic literature search according to PRISMA criteria was made by using two main databases. Only studies published up until to October 2022 in the English language with ≥10 enrolled patients were selected. Seven studies including 326 pts, of whom 201 (61.6%) harboring DDR defects, were selected. The majority of selected papers were retrospective and four out of seven (57.1%) had small sample size (<50 pts). Three out of seven (42.8%) studies reported a more favorable outcome (overall or progression free survival) after therapy with alpha emitters (223Ra-therapy or [225Ac]Ac-PSMA-617) in subjects with DDR defects with respect to those without mutations. In two studies employing alpha or beta emitters ([177Lu]/[225Ac]-PMSA), no significant benefit was registered in pts harboring DDR defects. In all but one paper, no significant difference in response rate was reported among pts with or without DDR mutations. Although preliminary and biased by the retrospective design, preliminary data suggest a trend towards a longer survival in PCa pts harboring DDR defects submitted to radionuclide targeted therapy with alpha emitters.

Fibromyalgia (FM) represents a condition that is still controversial in its entity, pathophysiology, diagnosis and management. The aim of this review is to focus on imaging aspects of FM, especially on novel approaches in molecular imaging, with a special focus on neuroimaging. Novel functional and molecular imaging findings may represent, eventually, future biomarkers both in research settings and in terms of clinical practice. Several imaging techniques have already been tested in clinical trials in the FM field, including functional MRI, positron emission tomography (PET) imaging with 18 F-FDG in FM, PET imaging of the dopaminergic system, PET imaging of the GABAergic system, PET imaging with neuroinflammation and neuroimmune parameters, PET imaging of the opioid system and H 2 15 O-PET activation studies. Therefore, the potential role in the FM field of fMRI and different PET tracers has been discussed in different settings, serving as a comprehensive guide of novel imaging options both in research and in the clinical field.

Introduction: Prostate-specific membrane antigen (PSMA) has emerged as a highly relevant target for prostate cancer (PC) diagnosis and therapy. PSMA inhibitors targeting PSMA-enzymatic domain have been successfully labeled with radionuclides emitting positrons or gamma-photons, thus obtaining tracers suitable for imaging with positron emission computed tomography (PET/CT) or single-photon emission tomography (SPECT)., Areas Covered: The different approaches for obtaining PSMA-ligands labeled with gamma-emitting nuclides ( 99m Tc or 111 In) are reviewed. Furthermore, the applications of 99m Tc/ 111 In-PSMA SPECT for the imaging of PC patients in different clinical settings (staging or biochemical recurrence) are covered. Lastly, the employment of PSMA-targeted SPECT tracers for radioguided surgery (RGS) during primary or salvage lymphadenectomy is discussed., Expert Opinion: RGS provided satisfying preliminary results in both primary and salvage lymphadenectomy, allowing to discriminate between pathological and non-pathological nodes with high accuracy, although prospective studies with larger cohorts are needed to further validate this surgical approach. The potential of PSMA-targeted SPECT/CT has not been fully explored yet, but it might represent a relatively cost-effective alternative to PSMA PET/CT in limited resource environments. In this perspective, the implementation of novel SPECT technologies or algorithms, such as semiconductor-ionization detectors or resolution recovery reconstruction, will be topic of future investigation.

Introduction: Prostate and breast cancer represent a leading cause of cancer-related death worldwide with a dramatic social and demographic impact. Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, have been found overexpressed in both the aforementioned malignancies, and have emerged as a potentially useful target to combine imaging and therapy in a unique, synergistic approach, namely 'theranostics.', Areas Covered: The biological characteristics of GRPRs, as well as their aberrant expression in breast and prostate cancer, are covered. Furthermore, the role of the different available GRPR agonists and antagonists, labeled with radionuclides suitable for molecular imaging through single photon computed tomography (SPECT) or positron emission computed (PET/CT), is reviewed, with a particular focus on the potential theranostic implications., Expert Opinion: GRPR-targeted molecular imaging of breast and prostate cancer gave promising results in pre-clinical studies. Notably, GRPRs' expression was found to be inversely correlated with disease progression in both prostate and breast cancer. Among the different GRPR agonists and antagonists applied as imaging probes, RM26 presented particularly interesting applications, with meaningful theranostic potential, but its diagnostic performance resulted highly influenced by the choice of the chelator-radionuclide complex, being long-life radionuclides more suitable for obtaining high-contrast imaging.

Purpose: Breast cancer is the most common solid tumor and the second highest cause of death in the United States. Detection and diagnosis of breast tumors includes various imaging modalities, such as mammography (MMG), ultrasound (US), and contrast-enhancement MRI. Breast-specific gamma imaging (BSGI) is an emerging tool, whereas morphological imaging has the disadvantage of a higher absorbed dose. Our aim was to assess if this imaging method is a more valuable choice in detecting breast malignant lesions compared to morphological counterparts., Methods: research on Medline from 1995 to June 2022 was conducted. Studies that compared at least one anatomical imaging modality with BSGI were screened and assessed through QUADAS2 for risk of bias and applicability concerns assessment. Sensitivity, specificity, positive and negative predictive value (PPV and NPV) were reported., Results: A total of 15 studies compared BSGI with MMG, US, and MRI. BSGI sensitivity was similar to MRI, but specificity was higher. Specificity was always higher than MMG and US. BSGI had higher PPV and NPV. When used for the evaluation of a suspected breast lesion, the overall sensitivity was better than the examined overall sensitivity when BSGI was excluded. Risk of bias and applicability concerns domain showed mainly low risk of bias., Conclusion: BSGI is a valuable imaging modality with similar sensitivity to MRI but higher specificity, although at the cost of higher radiation burden., Competing Interests: The authors declare no conflict of interest.

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine ( 123 I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123 I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words "MIBG", "metaiodobenzylguanidine", "heart", "spect", and "tomographic". The included studies had to correlate 123 I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123 I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123 I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123 I-mIBG planar myocardial imaging., (© 2021. The Author(s).)

The most frequent thyroid cancer is Differentiated Thyroid Cancer (DTC) representing more than 95% of cases. A suitable choice for the treatment of DTC is the systemic administration of 131-sodium or potassium iodide. It is an effective tool used for the irradiation of thyroid remnants, microscopic DTC, other nonresectable or incompletely resectable DTC, or all the cited purposes. Dosimetry represents a valid tool that permits a tailored therapy to be obtained, sparing healthy tissue and so minimizing potential damages to at-risk organs. Absorbed dose represents a reliable indicator of biological response due to its correlation to tissue irradiation effects. The present paper aims to focus attention on iodine therapy for DTC treatment and has developed due to the urgent need for standardization in procedures, since no unique approaches are available. This review aims to summarize new proposals for a dosimetry-based therapy and so explore new alternatives that could provide the possibility to achieve more tailored therapies, minimizing the possible side effects of radioiodine therapy for Differentiated Thyroid Cancer.

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.

Background: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration., Methods: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided., Results: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression., Conclusions: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile.