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The main aim of this preliminary in vitro study was to evaluate both the uptake of [ 99 Tc]Sestamibi into prostate cancer cells and the relationship among [ 99 Tc]Sestamibi bioaccumulation, cancer cells proliferation and apoptosis. An in vitro study in which PC3 prostate cancer cell line was cultured with increasing doses of decayed sestamibi has been developed. Specifically, PC3 cells were incubated with three different concentrations of [ 99 Tc]Sestamibi: 10 µg/mL, 1 µg/mL, and 0.1 µg/mL Expression of apoptotic caspase-3 and AIF, as well as the ultrastructure of PC3 cells, were evaluated at T0 and after 24, 48, 72, and 120 h following [ 99 Tc]Sestamibi incubation. Data here reported showed the bioaccumulation of sestamibi in prostate cancer cells. As concern the cancer cell homeostasis, the treatment of PC3 cells with [ 99 Tc]Sestamibi strongly influenced the cells proliferation. Indeed, a significant reduction in the number of mitosis was observed. Noteworthy, the accumulation of sestamibi in prostate cancer cells was associated with the appearance of morphological signs of apoptosis. The increase in AIF and caspase 3 expression in prostate cancer cells treated with 10 µg/mL of [ 99 Tc]Sestamibi confirmed that this radiopharmaceutical can trigger the apoptosis. To the best of our knowledge, this preliminary study reported for the first time in vitro data about the uptake of sestamibi in prostate cancer cells. The evidence about the accumulation of sestamibi in prostate cancer cells and its role in the apoptosis process could open new clinical perspectives on the use of this radiopharmaceutical in both the diagnosis and treatment of prostate cancers., (© 2022. The Author(s).)

Background: The diagnosis of coronary artery disease (CAD) remains challenging. It is uncertain whether hybrid imaging can improve diagnostic accuracy for CAD., Methods: This is a systematic review and multivariate meta-analysis. We searched PubMed and The Cochrane Library for recent (≥ 2010) systematic reviews of diagnostic test accuracy studies on non-invasive imaging for CAD. Study-level data were extracted from them, and pooled with pairwise and multivariate meta-analytic methods, using invasive coronary angiography (ICA) or invasive fractional flow reserve (FFR) as reference standards, focusing on sensitivity and specificity., Results: Details from 661 original studies (71,823 patients) were pooled. Pairwise meta-analysis using ICA as reference showed that anatomic imaging was associated with the best diagnostic accuracy (sensitivity = 0.95 [95% confidence interval 0.94-0.96], specificity = 0.83 [0.81-0.85]), whereas using FFR as reference identified hybrid imaging as the best test (sensitivity = 0.87 [0.83-0.90], specificity = 0.82 [0.76-0.87]). Multivariate meta-analysis confirmed the superiority of anatomic imaging using ICA as reference (sensitivity = 0.96, specificity = 0.83), and hybrid imaging using FFR as reference (sensitivity = 0.88 [0.86-0.91], specificity = 0.82 [0.77-0.87])., Conclusions: Non-invasive hybrid imaging tests appear superior to anatomic or functional only tests to diagnose ischemia-provoking coronary lesions, whereas anatomic imaging is best to diagnose and/or rule out angiographically significant CAD., Systematic Review Registration: PROSPERO Registry Number CRD42018088528.

This study was aimed at evaluating whether transient dipyridamole-induced myocardial ischemia in hypertensive patients reflects on endothelin-1 plasma levels by comparing normotensives and hypertensives with or without stable angina. Endothelin-1 plasma levels were assessed in baseline conditions and after provocative stress test by dipyridamole. Four groups of ten age- and sex-matched subjects were retrospectively considered among patients referred for chest pain evaluation and submitted to high-dose Dipyridamole Echocardiographic-Scintigraphic combined test (DES). On the basis of DES results we considered: (1) control normotensives subjects; (2) essential hypertensives (for both groups negative result of DES); (3) essential hypertensives with stable angina; and (4) normotensives with stable angina (for both groups concordant DES detection of myocardial ischemia). Our data showed a marked post-DES increase of endothelin-1 plasma levels in hypertensives with stable angina (mean levels = 16.50 ± 4.19 pg/ml p < 0.001 vs. baseline = 9.05 ± 1.37 pg/ml) and a minor increase in stable angina pts (mean levels = 8.3 ± 1.75 pg/ml p < 0.01 vs. baseline = 6.74 ± 0.61 pg/ml) whereas non significant increase was observed both in control (mean levels = 5.09 ± 0.83 pg/ml p = n.s. vs. baseline = 4.91 ± 1.04 pg/ml) and hypertensives groups (mean levels = 6.34 ± 1.72 pg/ml p = n.s. vs. baseline = 5.95 ± 1.04 pg/ml). ET-1 involvement in hypertension-related ischemic heart disease patho-physiology appears to be considered.

Coronary artery disease (CAD) is the most common and important cause of ischemic heart disease, with major implications on global morbidity and mortality. Non-invasive testing is crucial in the diagnostic and prognostic work-up of patients with or at risk of CAD, and also to guide decision making in terms of pharmacologic and revascularization therapy. The traditional paradigm is to view anatomic (i.e., coronary computed tomography) and functional imaging (e.g., myocardial perfusion scintigraphy) tests as opposing alternatives. Such approach is too reductionist and does not capitalize on the strengths of each type of test while risking to overlook the inherent limitations. The combination of anatomic and functional tests in a logic of hybrid imaging holds the promise of overcoming the limitations inherent to anatomic and functional testing, enabling more accurate diagnosis, prognosis, and guidance for revascularization in patients with CAD.

Purpose: The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[ 18 F]fluoro -D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[ 18 F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [ 18 F]FBB) in a group of patients affected by Alzheimer's disease (AD)., Procedures: We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [ 18 F]FDG and [ 18 F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [ 18 F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [ 18 F]FDG PET/CT scans., Results: SPM analysis in AD patients showed a significant negative correlation between [ 18 F] FBB and [ 18 F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group., Conclusions: Combined imaging with [ 18 F]FBB and [ 18 FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

Background: Myocardial perfusion imaging (MPI) has an established role in the work-up of coronary artery disease (CAD), but its comparative accuracy is debated in elderly patients. We examined a large administrative database to appraise the performance of MPI in octogenarians., Methods: Our institutional database was queried for patients undergoing MPI without recent coronary revascularization or myocardial infarction (MI). We compared baseline, procedural, diagnostic, and prognostic features in patients aged < 80 vs ≥ 80 years with bivariate and propensity-adjusted analyses., Results: From 13,254 patients, 12,737 (96.1%) were < 80 years old and 517 (3.9%) ≥ 80 years. Octogenarians were less likely to undergo exercise testing, had more severe and extensive myocardial ischemia (all P < 0.001), whereas CAD was more prevalent and diffuse in them (P = 0.012), and major adverse cardiac events more common during follow-up (P = 0.009). Diagnostic accuracy of MPI was similar or higher in octogenarians than in younger patients (e.g., sensitivity for three-vessel disease 92% in octogenarians vs 91% in younger patients), as was prognostic accuracy. Using propensity-matched analyses, MPI again yielded satisfactory prognostic accuracy in octogenarians., Conclusions: Use of MPI in octogenarians is associated with similar or better prognostic accuracy than in younger subjects.

Background: Myocardial necrosis after myocardial infarction (MI) is common; extent and severity are however variable. The pattern is recognized by myocardial perfusion imaging (MPI) as fixed perfusion defects (FPD). The fate of such FPD is not well appraised. This study addressed this important issue in a large number of patients undergoing serial MPI in relation to type of intervening therapy., Methods: Patients with prior MI or MPI-evidence of myocardial necrosis undergoing serial MPI without intervening acute coronary syndromes were included. The fate of necrosis by MPI on per-patient and per-region analysis was analyzed, factoring also the impact of intervening coronary revascularization (CR)., Results: A total of 3691 patients with 25,837 regions were identified, including 1413 (38.3%) subjects with 3358 (13.0%) regions exhibiting necrosis. Serial MPI after 29±21 months confirmed the persistent presence of myocardial necrosis FPD in the vast majority of patients and regions (86%); the consistency was even higher in the presence of moderate or severe necrosis (99%). Neither type nor site of CR significantly impacted on the presence and extent of myocardial necrosis at multivariable analysis., Conclusions: The finding of myocardial necrosis by MPI remains highly consistent over time, and is not significantly altered by CR.

Background: Randomized trials have challenged the role of revascularization in stable coronary artery disease. We aimed to appraise the impact of revascularization on ischemia in patients undergoing serial myocardial perfusion scintigraphy (MPS)., Methods: We queried our institutional database for stable subjects undergoing serial MPS and appraised the impact of revascularization on changes in ischemia., Results: A total of 3631 patients were included: 967 (27%) undergoing revascularization and 2664 (73%) receiving medical therapy only. Patients treated with revascularization had a significantly lower burden of myocardial ischemia at follow-up (odds ratio = 0.577 [95% confidence interval 0.483-0.689] vs medical therapy, P < .001). Among all those having moderate or severe ischemia at baseline, revascularization was associated with a follow-up prevalence of 80% for no, minimal, or mild ischemia and 20% for moderate or severe ischemia, vs 43% and 57% for medical therapy (P < .001). Even at multivariable analysis and propensity-adjusted, and propensity-matched analyses, revascularization was associated with a significantly lower prevalence of moderate or severe ischemia at follow-up (respectively P < .001, P = .001, and P = .042)., Conclusions: Revascularization appears superior to medical therapy in reducing ischemic burden and normalizing myocardial perfusion among subjects with moderate or severe ischemia at baseline.

Background: Myocardial perfusion scintigraphy (MPS) has an established diagnostic and prognostic role in patients with or at risk for coronary artery disease, with ischemia severity and extent having already been identified as key predictors. Whether this is affected by the location of myocardial ischemia is uncertain. We aimed at comparing the prognostic outlook of patients undergoing MPS according to the site of ischemia., Methods: Our institutional database was queried for subjects undergoing MPS, without myocardial necrosis or recent revascularization. We focused on the prognostic impact of location of vessel-related ischemia (VRI) at MPS, distinguishing four mutually exclusive groups: single-VRI involving left anterior descending (LAD), single-VRI not involving LAD, multi-VRI involving LAD, and multi-VRI not involving LAD. The primary outcome was the long-term (>1 year) rate of death or myocardial infarction (D/MI)., Results: A total of 13,254 patients were included. Moderate or severe VRI occurred in 2,627 (20%) patients. Clinical outcomes were significantly different among the groups of patients with moderate or severe VRI, including death, cardiac death, non-fatal myocardial infarction or their composites (overall P < .001). Specifically, and excluding subjects undergoing revascularization as first follow-up event, D/MI occurred in 8.4% of patients with single-VRI involving LAD, 5.5% of subjects with single-VRI not involving LAD, 16.5% of those with multi-VRI involving LAD, and 7.3% of patients with multi-VRI not involving LAD (overall P < .001). Even at incremental multivariable Cox proportional analysis, hierarchical VRI was independently associated with an increased risk of D/MI [hazard ratio = 1.17 (1.04-1.08) for each class increment, P = .010]., Conclusions: Location and extent of myocardial ischemia at MPS according to the VRI concept have a hierarchical predictive impact, with multi-VRI involving LAD being significantly and independently more prognostically ominous than other types of VRI.

(90)Y radioembolization and peptide-receptor radionuclide therapy (PRRT) with(177)Lu-DOTATATE are both effective treatments for patients with inoperable neuroendocrine metastatic tumors (NET). We report the case of a 72-year-old man with severe functional syndrome due to a metastatic NET. (68)Ga-DOTATOC positron-emission tomography (PET) revealed high somatostatin receptor expression in a gross liver metastasis, in one abdominal lymph node and in several skeletal lesions. The patient underwent liver radioembolization with (90)Y-resin microspheres followed by four cycles of PRRT with(177)Lu-DOTATATE. After 3 months, a complete remission of the functional syndrome was observed. (68)Ga-DOTATOC PET demonstrated a complete response for skeletal and lymph nodal lesions with a residual bulky mass in the liver. Therefore a further (90)Y radioembolization was performed as consolidation treatment for the hepatic lesion. Six months after these combined treatments, (68)Ga-DOTATOC PET demonstrated complete metabolic response in liver and stable extrahepatic lesions. No significant long-term adverse reactions were registered. To our knowledge, the sequential use of (90)Y radiembolization before and after PRRT in a liver-dominant advanced NET has not been reported in the literature and this case suggests that these combined treatments can be safe and effective.

Background: Myocardial perfusion scintigraphy (MPS) represents a key prognostic tool, but its predictive yield is far from perfect. We developed a novel clinically relevant segmentation method and a corresponding maximal ischemia score (MIS) in order to risk-stratify patients undergoing MPS., Methods: Patients referred for MPS were identified, excluding those with evidence of myocardial necrosis or prior revascularization. A seven-region segmentation approach was adopted for left ventricular myocardium, with a corresponding MIS distinguishing five groups (no, minimal, mild, moderate, or severe ischemia). The association between MIS and clinical events was assessed at 1 year and at long-term follow-up., Results: A total of 8,714 patients were included, with a clinical follow-up of 31 ± 20 months. Unadjusted analyses showed that subjects with a higher MIS were significantly different for several baseline and test data, being older, having lower ejection fraction, and achieving lower workloads (P < .05 for all). Adverse outcomes were also more frequent in patients with higher levels of ischemia, including cardiac death, myocardial infarction (MI), and their composites (P < .05 for all). Differences in adverse events remained significant even after extensive multivariable adjustment (hazard ratio for each MIS increment = 1.57 [1.29-1.90], P < .001 for cardiac death; 1.19 [1.04-1.36], P = .013 for MI; 1.23 [1.09-1.39], P = .001 for cardiac death/MI)., Conclusions: Our novel segmentation method and corresponding MIS efficiently yield satisfactory prognostic information.

Background: The clinical impact of extrapleural pneumonectomy in malignant pleural mesothelioma is poorly investigated., Methods: Between 1997 and 2007, 29 consecutive patients underwent extrapleural pneumonectomy for mesothelioma and adjuvant chemoradiotherapy. Function (spirometry, arterial blood gas analysis, 6-min walk test, and echocardiographic fraction ejection estimation), symptoms (quantification of pain, dyspnea, cough, fever, weight loss, and Karnofsky performance status) and quality of life [Medical Outcomes Study Short Form, 36 item (SF-36) and St. George's Respiratory Questionnaire] were timely evaluated. Data were prospectively collected and retrospectively reviewed., Results: Only one postoperative death occurred. 30-day postoperative morbidity was 41%. Median survival was 19.5 months with 17 patients still alive at 1 year and 10 at 2 years, respectively. At 3 months, the expected decrement of forced expiratory volume in 1 s (P = 0.06) and forced vital capacity (P = 0.09) was not significant. Conversely, arterial blood gas, 6-min walk test, cardiac fraction ejection, pain (P < 0.05), dyspnea (P < 0.01), cough (P < 0.05), fever (P < 0.01), weight loss (P < 0.01), performance status (P < 0.01), SF-36 physical (P < 0.01), SF-36 mental (P < 0.05), St. George's Respiratory Questionnaire symptom (P < 0.01), activity (P < 0.05), and impact on mood (P < 0.05) improved. At 12 months, the amelioration of pain, dyspnea, performance status, and physical-related quality of life parameters remained stable. Thereafter, all parameters progressively deteriorated, although pain and dyspnea still persisted above the baseline values even after 24 months in all survivors. Postoperative improvement of pain (P = 0.04), dyspnea (P = 0.04), 6-min walk test (P = 0.03), and SF-36 physical (P = 0.04) and mental (P = 0.03) components were positive prognosticators., Conclusions: Extrapleural pneumonectomy has a significant and durable impact on function and symptoms as well as on physical and mental components of quality of life in patients with malignant pleural mesothelioma.