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Neuroblastoma, the most common extracranial solid tumor in children, accounts for nearly 8% of childhood cancers in the United States. It is a disease with pronounced clinical and biological heterogeneities. The amplification of MYCN, whose key tumorigenic functions include the promotion of proliferation, facilitation of the cell's entry into the S phase, and prevention of cells from leaving the cell cycle, correlates with poor prognosis. Patients with a high proliferation index disease have low survival rates. Neuroblastoma is one of the most radioresponsive of all human tumors. To exploit this radiosensitivity, radioactive guanidine (R)‐(–)‐5‐[125I]iodo‐3′‐O‐[2‐(ε‐guanidinohexanoyl)‐2‐phenylacetyl]‐2′‐deoxyuridine (9, GPAID) was designed. This compound enters neuroblastoma cells much like metaiodobenzylguanidine (MIBG). Additionally, it cotargets DNA of proliferating cells, an attribute especially advantageous in the treatment of MYCN‐amplified tumors. GPAID was synthesized from the trimethylstannyl precursor with an average yield of >90% at the no‐carrier‐added specific activities. The norepinephrine transporter‐aided delivery of GPAID to neuroblastoma cells was established in the competitive uptake studies with nonradioactive MIBG. The intracellular processing and DNA targeting properties were confirmed in the subcellular distribution experiments. Studies in a mouse model of neuroblastoma demonstrated the therapeutic potential of GPAID. The tin precursor of GPAID can be used to prepare compounds radiolabeled with single‐photon emission computed tomography (SPECT)‐ and positron‐emission tomography (PET)‐compatible radionuclides. Accordingly, these reagents can function as theranostics useful in the individualized and comprehensive treatment strategies comprising treatment planning and the assessment of tumor responses as well as the targeted molecular radiotherapy employing treatment doses derived from the imaging data. [ABSTRACT FROM AUTHOR]

Currently, many scientific fields such as psychology or biomedicine face a methodological crisis concerning the reproducibility, replicability, and validity of their research. In neuroimaging, similar methodological concerns have taken hold of the field, and researchers are working frantically toward finding solutions for the methodological problems specific to neuroimaging. This article examines some ethical and legal implications of this methodological crisis in neuroimaging. With respect to ethical challenges, the article discusses the impact of flawed methods in neuroimaging research in cognitive and clinical neuroscience, particularly with respect to faulty brain-based models of human cognition, behavior, and personality. Specifically examined is whether such faulty models, when they are applied to neurological or psychiatric diseases, could put patients at risk, and whether this places special obligations on researchers using neuroimaging. In the legal domain, the actual use of neuroimaging as evidence in United States courtrooms is surveyed, followed by an examination of ways that the methodological problems may create challenges for the criminal justice system. Finally, the article reviews and promotes some promising ideas and initiatives from within the neuroimaging community for addressing the methodological problems. [ABSTRACT FROM PUBLISHER]

Objective: To examine factors associated with bone scan use in patients undergoing radical cystectomy and to assess trends in use over time.Materials and Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified 5573 patients who underwent radical cystectomy from 2004 to 2011. The primary outcome was completion of a bone scan within 6 months prior to surgery. Demographic, regional, and clinicopathologic predictors of bone scan use were examined using a mixed logit model with health service area as a random effect.Results: Among radical cystectomy patients, 1754 (31%) completed a preoperative bone scan. Urologists ordered most of these studies (69%). The adjusted probability of a patient undergoing a bone scan decreased from 0.40 in 2004 to 0.29 in 2011 (P = .01). Compared with patients in the northeast region, those in the south, central, and west regions were less likely to have a bone scan (P <.001). Compared with those with stage ≤T1, patients with higher stage disease were more likely to have a bone scan (P <.001). Among the highest volume surgeons, there was significant variation in the proportion of patients who completed preoperative bone scans (P < .001).Conclusion: Despite a recent decline, bone scans are used frequently in the preoperative staging of bladder cancer. Although some clinical factors are associated with bone scan use, significant regional and provider variation suggest areas to improve standardization of practice. [ABSTRACT FROM AUTHOR]

Background: Much remains unknown about experiences, including working activities and pay, of women in cardiology, which is a predominantly male specialty. Objectives: The goal of this study was to describe the working activities and pay of female cardiologists compared with their male colleagues and to determine whether sex differences in compensation exist after accounting for differences in work activities and other characteristics. Methods: The personal, job, and practice characteristics of a national sample of practicing cardiologists were described according to sex. We applied the Peters-Belson technique and multivariate regression analysis to evaluate whether gender differences in compensation existed after accounting for differences in other measured characteristics. The study used 2013 data reported by practice administrators to MedAxiom, a subscription-based service provider to cardiology practices. Data regarding cardiologists from 161 U.S. practices were included, and the study sample included 2,679 subjects (229 women and 2,450 men). Results: Women were more likely to be specialized in general/noninvasive cardiology (53.1% vs. 28.2%), and a lower proportion (11.4% vs. 39.3%) reported an interventional subspecialty compared with men. Job characteristics that differed according to sex included the proportion working full-time (79.9% vs. 90.9%; p < 0.001), the mean number of half-days worked (387 vs. 406 days; p = 0.001), and mean work relative value units generated (7,404 vs. 9,497; p < 0.001) for women and men, respectively. Peters-Belson analysis revealed that based on measured job and productivity characteristics, the women in this sample would have been expected to have a mean salary that was $31,749 (95% confidence interval: $16,303 to $48,028) higher than that actually observed. Multivariate analysis confirmed the direction and magnitude of the independent association between sex and salary. Conclusions: Men and women practicing cardiology in this national sample had different job activities and salaries. Substantial sex-based salary differences existed even after adjusting for measures of personal, job, and practice characteristics. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, 99mTc sestamibi and 99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. 123I has a similar energy as 99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an 123I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: 123I-CMICE-013 was synthesized by radiolabeling rotenone with 123I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60°C for 45min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10mM NaOAc pH 6.5. The inactive analog 127I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2h (n =6) and 24h (n =8) post injection (p.i.). Results: 123I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111GBq/μmol; 400–3000mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2h p.i. showed significant myocardial uptake (2.01±0.48%ID/g) and high heart to liver (2.98±0.93), heart to lung (4.11±1.04) and heart to blood (8.37±3.97) ratios. At 24h p.i., the majority of 123I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: 123I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics. [ABSTRACT FROM AUTHOR]

Purpose: Myocardial perfusion imaging contributes >20 % of the average medical radiation exposure to the population in the USA. Imaging protocols able to achieve a radiation exposure ≤9 mSv in 50 % of the studies by 2014 have been recommended. The aim of this study was to analyse the temporal evolution of administered activities in patients scheduled for dual-day Tc tracer gated single photon emission computed tomography (SPECT) and to compare different dose administration protocols in terms of patients' effective dose. Methods: Patients evaluated from 1 July 2002 to 31 January 2012 were allocated according to the protocol adopted: group 1: fixed activity according to diagnostic reference level: 740 MBq up to 80 kg (adapted for weight <60 kg); 900 MBq 80-100 kg, 1,110 MBq >100 kg, standard filtered back-projection (FBP) reconstruction; group 2: weight-adjusted activity: 8 MBq/kg up to 1,110 MBq, standard FBP reconstruction; and group 3: 4 MBq/kg, UltraSPECT wide beam reconstruction (WBR) reconstruction. A dual-head Anger camera (GE Helix) was used. Results: A total of 9,060 patients were allocated to different groups: 4,751 in group 1, 2,844 in group 2 and 1,465 in group 3. The stress + rest administered activity was 1,617 ± 180 in group 1, 1,136 ± 260 in group 2 and 682 ± 164 MBq in group 3 (all p < 0.001). Patients' effective dose was 13.7 ± 3 in group 1, 9.5 ± 2.8 in group 2 and 5.7 ± 1.6 mSv in group 3 (all p < 0.001). The 50th percentile was 12.6 in group 1, 9.1 in group 2 and 5.3 mSv in group 3. The effective dose received by the dedicated cardiologists was 2.1, 1.5 and 1.0 μSv/exam in group 1, group 2 and group 3 periods, respectively (all p < 0.001). Conclusion: A significant reduction over time in the administered activity for gated SPECT was achieved; accordingly, a significant reduction in patients' exposure was obtained. A simple weight-adjusted strategy with 8 MBq/kg immediately fulfils the recommendations to limit exposure. In selected group 3 patients, a stress-only strategy allows for studies with <3 mSv exposure. Thus, at least the adoption of a new reconstruction algorithm is strongly encouraged, and suggested tracer activities for cardiac gated SPECT are to be revised. [ABSTRACT FROM AUTHOR]

Background: Perfusion-cardiovascular magnetic resonance (CMR) is generally accepted as an alternative to SPECT to assess myocardial ischemia non-invasively. However its performance vs gated-SPECT and in sub-populations is not fully established. The goal was to compare in a multicenter setting the diagnostic performance of perfusion-CMR and gated-SPECT for the detection of CAD in various populations using conventional x-ray coronary angiography (CXA) as the standard of reference. Methods: In 33 centers (in US and Europe) 533 patients, eligible for CXA or SPECT, were enrolled in this multivendor trial. SPECT and CXA were performed within 4 weeks before or after CMR in all patients. Prevalence of CAD in the sample was 49% and 515 patients received MR contrast medium. Drop-out rates for CMR and SPECT were 5.6% and 3.7%, respectively (ns). The study was powered for the primary endpoint of non-inferiority of CMR vs SPECT for both, sensitivity and specificity for the detection of CAD (using a single-threshold reading), the results for the primary endpoint were reported elsewhere. In this article secondary endpoints are presented, i.e. the diagnostic performance of CMR versus SPECT in subpopulations such as multi-vessel disease (MVD), in men, in women, and in patients without prior myocardial infarction (MI). For diagnostic performance assessment the area under the receiver-operator-characteristics-curve (AUC) was calculated. Readers were blinded versus clinical data, CXA, and imaging results. Results: The diagnostic performance (= area under ROC = AUC) of CMR was superior to SPECT (p = 0.0004, n = 425) and to gated-SPECT (p = 0.018, n = 253). CMR performed better than SPECT in MVD (p = 0.003 vs all SPECT, p = 0.04 vs gated-SPECT), in men (p = 0.004, n = 313) and in women (p = 0.03, n = 112) as well as in the non-infarct patients (p = 0.005, n = 186 in 1-3 vessel disease and p = 0.015, n = 140 in MVD). [ABSTRACT FROM AUTHOR]

Background: Much of our understanding of gender differences in chest pain was derived from noncontemporary reports. The aim of the current report was to compare the frequency of chest pain by measures of ischemia in 824 women with suspected myocardial ischemia prospectively enrolled in a clinical trial of exercise testing with electrocardiography (ETT-ECG) alone compared to myocardial perfusion single photon emission computed tomography (SPECT) (ETT-MPS). Methods: Women seeking evaluation of chest pain or anginal equivalent symptoms were randomized to ETT-ECG or ETT-MPS with Tc-99m tetrofosmin. The Women's Ischemia Syndrome Evaluation (WISE) and Seattle Angina Questionnaire (SAQ) chest pain and Duke Activity Status Index (DASI) questionnaires were employed in enrolled women. Higher SAQ scores denote improved symptoms or functioning. Results: Eight hundred twenty-four women, average age 63 years, at intermediate-high coronary artery disease (CAD) likelihood were enrolled from 43 North American centers. Traditional cardiac risk factors were prevalent, with nearly half of women having a family history of premature coronary disease, hypertension, and hyperlipidemia. Chest pain symptoms occurring at least one to three times per week were reported in 60% of women. An examination of the SAQ domains revealed that although women reported minimal physical limitations (median, interquartile range [IQR] 88, 75-100), there was a greater frequency of stable chest pain symptoms (median, IQR=40, 30-50). The majority of women (79%) reported moderate to heavy physical activity levels at home, with the average ETT and DASI estimated metabolic equivalents (METs) of 8.6±2.6 and 11.5±3.8. Women with more frequent daily episodes of chest pain were more likely to have a lower Duke Treadmill Score (DTS), 1 or mm of ST segment depression, and an abnormal MPS. Conclusions: The current report details a contemporary evaluation of female-specific symptomatology and measures of myocardial ischemia. Women reporting frequent angina were more likely to exhibit ischemia and this may characterize a female-specific typical angina pattern. [ABSTRACT FROM AUTHOR]

Abstract: Background: The high rate of comorbidity of tobacco smoking with alcohol drinking suggests common neural substrates mediate the two addictive disorders. The beta2*-containing nicotinic acetylcholine receptor (β2*-nAChR) has recently emerged as a prime candidate because some alpha and beta subunit genes have been linked to alcohol consumption and alcohol use behaviors. We hypothesized that β2*-nAChR availability would be altered by alcohol in heavy drinking nonsmokers. Methods: Eleven heavy drinking (mean age 39.6±12.1 years) and 11 age and sex-matched control (mean age 40.8±14.1 years) nonsmokers were imaged using [123I]5-IA-85380 ([123I]5-IA) single photon emission computed tomography (SPECT). Heavy alcohol drinkers drank varied amounts of alcohol (70–428/month) to facilitate exploratory linear analyses of the possible effects of alcohol. Results: Heavy drinkers consumed on average 9.1±7.3 drinks/occasion; whereas controls drank 1.2±0.9 drinks/occasion. Heavy drinkers were imaged 2.0±1.6 days after last alcoholic beverage. Overall, there were no significant differences in β2*-nAChR availability between the heavy drinking and control nonsmokers. Exploratory analyses of other factors that may be uniquely regulated by alcohol suggested no effects of age, number of alcohol drinks, years drinking, severity of drinking, craving or withdrawal. Conclusions: These preliminary analyses do not suggest a decrease in receptor availability in heavy drinking nonsmokers as compared to control nonsmokers. However, a larger study is warranted to explore effects of heavy alcohol drinking on other variables, such as sex, smoking, and genetic make up. [Copyright &y& Elsevier]

Vasodilator stress myocardial perfusion imaging (MPI) accounts for up to 50% of all stress MPI studies performed in the U.S. In 2008, the Food and Drug Administration approved regadenoson for stress testing in conjunction with MPI. Regadenoson, unlike adenosine, is a selective A2A agonist that is given as an intravenous bolus at a fixed dose, with less undesirable side effects including atrioventricular block and bronchospasm. Unlike adenosine, regadenoson could be used in patients with mild-to-moderate reactive airway disease. This review will summarize the pre-clinical and clinical data on regadenoson, as they specifically relate to its use as a vasodilator stress agent, currently the only approved selective A 2A agonist. [Copyright &y& Elsevier]

This article explores the admissibility of neuroimaging evidence in U.S. courts, recognizing various trends in decisions about such evidence. While courts have routinely admitted some neuroimages, such as CT scans and MRI, as proof of trauma and disease, they have been more circumspect about admitting the PET and SPECT scans and fMRI evidence. With the latter technologies, courts have often expressed reservations about what can be inferred from the images. Moreover, courts seem unwilling to find neuroimaging sufficient to prove either insanity or incompetency, but are relatively lenient about admitting neuroimages in death penalty hearings. Some claim that fMRI and “brain fingerprinting” are able to detect deception. Other scholars argue that brain fingerprinting is a dubious concept and that fMRI is not yet sufficiently reliable. Moreover, there are substantial concerns about privacy and the perils of mind reading implicit in such technology. Yet, there is a movement to try to make these new technologies “courtroom ready” in the near future, raising a host of legal, policy, and ethical questions to be answered. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]