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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]

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]

The article provides information on the impact of molecular imaging to medical, radiologic, and surgical practice. It states that molecular imaging allows clinicians to determine genetic factors that affect common diseases and identify individuals who will benefit most from disease screening procedures through physiology-based analysis. It also highlights the use of molecular imaging as an evaluation tool to evaluate the risk for diseases including cancer, heart disease, and diabetes.

Background: The effectiveness of stress single photon emission computed tomography (SPECT) as a gatekeeper for coronary angiography has not been extensively investigated. The characteristics of patients referred for early angiography after a normal stress SPECT study have not been described.Methods and Results: Over a 10-year period, 14,273 patients without documented coronary artery disease (CAD) underwent stress SPECT. Images were abnormal in 47% and normal in 53%. The overall survival rate at 15 years was 55% for patients with abnormal images versus 71% for those with normal images (P < .001). Early coronary angiography (< or =3 months) was performed in only 97 patients (1.3%) with normal SPECT studies versus 1,756 patients (26%) with abnormal SPECT studies (P < .001). Most patients with normal SPECT studies referred for early angiography (85%) had clinical, exercise, or scintigraphic findings worrisome for CAD. Two thirds of these highly selected patients with normal SPECT studies who underwent angiography did not have significant CAD; the remaining one third had primarily 1- and 2-vessel CAD.Conclusions: Stress SPECT is an effective gatekeeper for coronary angiography. The annual overall mortality rate for patients with normal images was 1.9%. Only 1.3% of patients with normal images were referred for early angiography. [ABSTRACT FROM AUTHOR]