Estrogen receptor (ER) status by immunohistochemistry (IHC) of cancer tissue is currently used to direct endocrine therapy in breast cancer. Positron emission tomography (PET) with 16α-18F-fluoro-17β-estradiol (18 F-FES) noninvasively characterizes ER ligand-binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18 F-FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a metaanalysis of published results comparing 18 F-FES PET and tissue assays of ER status in patients with breast cancer. PubMed and EMBASE were searched for English-language manuscripts with at least 10 patients and low overall risk of bias. Thresholds for imaging and tissue classification could differ between studies but had to be clearly stated. We used hierarchical summary receiver-operating characteristic curve models for the meta-analysis. The primary analysis included 113 nonbreast lesions from 4 studies; an expanded analysis included 327 total lesions from 11 studies. Treating IHC results as the reference standard, sensitivity was 0.78 (95% confidence region 0.65-0.88) and specificity 0.98 (0.65-1.00) for the primary analysis of nonbreast lesions. In the expanded analysis including non-IHC tissue assays and all lesion sites, sensitivity was 0.81 (0.73-0.87) and specificity 0.86 (0.68-0.94). These results suggest that 18 F-FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18 F-FES PET scans. This imaging assay has potential to improve clinically relevant outcomes for patients with (historically) ER-positive metastatic breast cancer, including those with brain metastases and/or lobular histology.

Several 8-arylimidazo[1,2-a]pyridines, 8-arylimidazo[1,5-a]pyridines, and 8-arylimidazo[1,5-a]pyridinones were prepared and tested in vitro for potential cardiac inotropic and electrophysiological activity. Selected analogues were further tested in vivo in canine hemodynamic and cardiac electrophysiology models. Compounds having an imidazole substituent consistently showed activity. A pharmacophoric relationship between heterocycle-phenyl-imidazole and positive inotropic activity was noted. The significance of this relationship is discussed.

SUMMARY Canine cardiac Purkinje fibers exposed Co sodiumfree solutions containing 16 m,\i CaCL, 20 mM tetraethvlammonium chloride, 108 m\i tetramethylammonium chloride, and 2.7 m\i KCI may be quiescent at a resting potential of either -5 0 mV or -9 0 mV. The membrane potential of these fibers can be switched from -50 mV to -90 mV by a hyperpolarizing current pulse and from -90 mV to -50 mV by a depolarizing current pulse. The transition from -50 mV to -90 raV depends on a voltage-dependent increase in potassium conductance, that conductance being low at -50 mV and high at -90 mV. A reduction in potassium conductance causes the fiber to depolarize from -9 0 mV to -5 0 mV because of the presence of an inward current which apparently is carried mainly by Ca. Fibers that show a high resting potential cannot be excited except by depolarizing stimuli strong enough to move the membrane from -9 0 mV to a threshold potential of about -4 0 raV. Fibers that show a low resting potential are more easily excited and may show rhythmic activity sustained by afterpotentials that appear only if the low membrane potential is accompanied by a low potassium conductance. Slow changes in membrane potential also are seen; these changes may result from movements of chloride.CARDIAC PURKINJE FIBERS bathed in Na-free solutions can show two stable resting potentials, one near -90 mV and one near -50 mV.1 2 We now report that within a critical range of [KJ 0 the membrane potential can be shifted from either level to the other by the application of hyperpolarizing or depolarizing current pulses. This transition appears to be governed primarily by a voltage-dependent change in potassium conductance, that conductance being high at the -9 0 mV level and low at the -5 0 mV level. This phenomenon assumes special interest because cardiac fibers can produce two distinct types of propagated action potentials. One type, dependent on a rapid increase in sodium conductance, is abolished by voltage-dependent inactivation when the resting potential is low. The other type, called the slow response, depends on an increase in permeability which occurs at membrane potentials between -5 0 and +10 mV. Various cardiac arrhythmias arise in fibers in which a loss of resting potential causes the rapid upstroke to be replaced by the slow response.' The possibility that cardiac fibers are characterized not only by an ability to produce two types of action potential, but also by an ability to display the two levels of resting potential from which those action potentials can arise, is therefore intriguing. MethodsMongrel dogs of either sex weighing 15-20 kg were anesthetized with an intravenous injection of pentobarbital sodium (30 mg/kg). The heart was rapidly excised and immersed in Tyrode's solution (Table 1). Bundles of Purkinje fibers (false tendons) 4-12 mm long were removed from the right and left ventricles, placed in a tissue bath, and perfused with Tyrode's solution at 36-37 c C. Fibers which, had a membrane potential of less than -8

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