Faculty Bibliography

OBJECTIVES/OBJECTIVE:Tc-labeled Annexin-V, which has a relative disadvantage of high radiation burden to nontarget organs. BACKGROUND:During apoptosis, the cell membrane phospholipids-phosphatidylserine (PS) and phosphatidylethanolamine (PE) are exposed and can be targeted by Annexin-V and Duramycin, respectively, for in vivo imaging. Identification of a reversible cell death process should permit therapeutic intervention to help reduce myocyte loss and left ventricle dysfunction. METHODS:Tc-Annexin-V (a positive tracer-control; n = 4) were intravenously administered 30 min after reperfusion. Of the 10 Duramycin group animals, 4 animals were treated with an antiapoptotic agent, minocycline at the time of reperfusion. In vivo and ex vivo micro-single-photon emission computed tomography (μSPECT) and micro-computed tomography (μCT) imaging was performed 3 h after reperfusion, followed by quantitative assessment of tracer uptake and pathological characterization. Fluorescent Duramycin and Annexin-V were injected in 4 rats to visualize colocalization in infarct areas in a 40-min left coronary artery occlusion and 30-min reperfusion model. RESULTS:Intense uptake of Duramycin and Annexin-V was observed in the apical (infarcted) areas. The percent injected dose per gram uptake of Duramycin in apical region (0.751 ± 0.262%) was significantly higher than remote area in same animals (0.045 ± 0.029%; p < 0.01). Duramycin uptake was insignificantly lower than Annexin-V uptake (1.23 ± 0.304%; p > 0.01) but demonstrated substantially lower radiation burden to kidneys (0.358 ± 0.210% vs. 1.58 ± 0.316%, respectively; p < 0.001). Fluorescence studies with Duramycin and Annexin V showed colocalization in infarct areas. Minocycline treatment substantially resolved Duramycin uptake (0.354% ± 0.0624%; p < 0.01). CONCLUSIONS:Duramycin is similarly effective in imaging apoptotic cell death as Annexin-V with lower nontarget organ radiation. Clinical feasibility of apoptosis imaging with a PE-seeking tracer should be tested.

Purpose In response to advances in the field, the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) recently updated their recommendations for molecular testing for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. Methods The molecular testing guideline was reviewed for developmental rigor by methodologists. Then an ASCO Expert Panel reviewed the content and the recommendations. Results The ASCO Expert Panel determined that the recommendations from the CAP/IASLC/AMP molecular testing guideline are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the guideline with minor modifications. Recommendations This update clarifies that any sample with adequate cellularity and preservation may be tested and that analytical methods must be able to detect mutation in a sample with as little as 20% cancer cells. It strongly recommends against evaluating epidermal growth factor receptor (EGFR) expression by immunohistochemistry for selection of patients for EGFR-targeted therapy. New for 2017 are recommendations for stand-alone ROS1 testing with additional confirmation testing in all patients with advanced lung adenocarcinoma, and RET, ERBB2 (HER2), KRAS, and MET testing as part of larger panels. ASCO also recommends stand-alone BRAF testing in patients with advanced lung adenocarcinoma. Recommendations are also provided for testing methods for lung cancers that have a nonadenocarcinoma non-small-cell component, for patients with targetable mutations who have relapsed on targeted therapy, and for testing the presence of circulating cell-free DNA. Additional information is available at www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

Cell death is desirable in cancer cells and undesirable in organs with limited regenerative potential, like the heart. Cell death comes in many forms, but only apoptosis and to a lesser degree necrosis is currently relevant to the clinical imager. Noninvasive imaging of cell death is an attractive option to understand pathophysiology, track disease activity, and evaluate response to intervention. Apoptosis seems to be the most promising target for imaging cell death, because it could be reversible and might be modulated with interventions. Molecular, nuclear, optical, or magnetic resonance imaging-based methods have been developed to identify intermediate steps in the apoptosis cascade. Animal studies show promising results for noninvasive imaging in various cardiovascular diseases. Human studies have shown feasibility, but clinical use is yet inconclusive. Newer technologies offer promise, especially for tracking apoptosis in evaluation of novel therapeutic interventions.

AIMS/OBJECTIVE:Atherosclerotic plaques vulnerable to rupture are almost always inflamed, and carry a large lipid core covered by a thin fibrous cap. The other components may include neovascularisation, intraplaque haemorrhage and spotty calcification. In contrast, stable plaques are characterised by a predominance of smooth muscle cells and collagen, and lipid core is usually deep seated or absent. This study is a proof of principle experiment to evaluate the feasibility of multiphoton microscopy (MPM) to identify aforementioned plaque components. METHODS AND RESULTS/RESULTS:MPM is a nonlinear optical technique that allows imaging based on intrinsic tissue signals including autofluorescence and higher-order scattering. In our study, MPM imaging was performed on morphologically diverse aortic and coronary artery plaques obtained during autopsy. Various histologically verified plaque components including macrophages, cholesterol crystals, haemorrhage, collagen and calcification were recognised by MPM. CONCLUSIONS:Recognition of the distinct signatures of various plaque components suggests that MPM has the potential to offer next-generation characterisation of atherosclerotic plaques. The higher lateral resolution (comparable to histology) images generated by MPM for identifying plaque components might complement larger field of view and greater imaging depth currently available with optical coherence tomography imaging. As the next step MPM would need to be evaluated for intact vessel imaging ex vivo and in vivo.