Survey of the potential environmental and health impacts in the immediate aftermath of the coal ash spill in Kingston, Tennessee.

An investigation of the potential environmental and health impacts in the immediate aftermath of one of the largest coal ash spills in U.S. history at the Tennessee Valley Authority (TVA) Kingston coal-burning power plant has revealed three major findings. First the surface release of coal ash with high levels of toxic elements (As = 75 mg/kg; Hg = 150 microg/kg) and radioactivity (226Ra + 228Ra = 8 pCi/g) to the environment has the potential to generate resuspended ambient fine particles (< 10 microm) containing these toxics into the atmosphere that may pose a health risk to local communities. Second, leaching of contaminants from the coal ash caused contamination of surface waters in areas of restricted water exchange, but only trace levels were found in the downstream Emory and Clinch Rivers due to river dilution. Third, the accumulation of Hg- and As-rich coal ash in river sediments has the potential to have an impact on the ecological system in the downstream rivers by fish poisoning and methylmercury formation in anaerobic river sediments.

D-Amino acid peptide residualizing agents bearing N-hydroxysuccinimido- and maleimido-functional groups and their application for trastuzumab radioiodination.

INTRODUCTION: Proteins that undergo receptor-mediated endocytosis are subject to lysosomal degradation, requiring radioiodination methods that minimize loss of radioactivity from tumor cells after this process occurs. To accomplish this, we developed the residualizing radioiodination agent N(ϵ)-(3-[(*)I]iodobenzoyl)-Lys(5)-N(α)-maleimido-Gly(1)-D-GEEEK (Mal-D-GEEEK-[(*)I]IB), which enhanced tumor uptake but also increased kidney activity and necessitates generation of sulfhydryl moieties on the protein. The purpose of the current study was to synthesize and evaluate a new D-amino acid based agent that might avoid these potential problems. METHODS: N(α)-(3-iodobenzoyl)-(5-succinimidyloxycarbonyl)-D-EEEG (NHS-IB-D-EEEG), which contains 3 D-glutamates to provide negative charge and a N-hydroxysuccinimide function to permit conjugation to unmodified proteins, and the corresponding tin precursor were produced by solid phase peptide synthesis and subsequent conjugation with appropriate reagents. Radioiodination of the anti-HER2 antibody trastuzumab using NHS-IB-D-EEEG and Mal-D-GEEEK-IB was compared. Paired-label internalization assays on BT474 breast carcinoma cells and biodistribution studies in athymic mice bearing BT474M1 xenografts were performed to evaluate the two radioiodinated D-peptide trastuzumab conjugates. RESULTS: NHS-[(131)I]IB-D-EEEG was produced in 53.8%±13.4% and conjugated to trastuzumab in 39.5%±7.6% yield. Paired-label internalization assays with trastuzumab-NHS-[(131)I]IB-D-EEEG and trastuzumab-Mal-D-GEEEK-[(125)I]IB demonstrated similar intracellular trapping for both conjugates at 1h ((131)I, 84.4%±6.1%; (125)I, 88.6%±5.2%) through 24h ((131)I, 60.7%±6.8%; (125)I, 64.9%±6.9%). In the biodistribution experiment, tumor uptake peaked at 48 h (trastuzumab-NHS-[(131)I]IB-D-EEEG, 29.8%±3.6%ID/g; trastuzumab-Mal-D-GEEEK-[(125)I]IB, 45.3%±5.3%ID/g) and was significantly higher for (125)I at all time points. In general, normal tissue levels were lower for trastuzumab-NHS-[(131)I]IB-D-EEEG, with the differences being greatest in kidneys ((131)I, 2.2%±0.4%ID/g; (125)I, 16.9%±2.8%ID/g at 144 h). CONCLUSION: NHS-[(131)I]IB-D-EEEG warrants further evaluation as a residualizing radioiodination agent for labeling internalizing antibodies/fragments, particularly for applications where excessive renal accumulation could be problematic.

Data-Driven Motion Detection and Characterization in PET Brain Scans Using List Mode

Head motion during a Positron Emission Tomography (PET) brain scan can considerably degrade image quality. External motion-tracking devices have proven successful in minimizing this effect, but the associated time, maintenance, and workflow changes inhibit their widespread clinical use. List-mode PET acquisition allows for the retroactive analysis of coincidence events on any time scale throughout a scan, and therefore potentially offers a data-driven motion detection and characterization technique. An algorithm was developed to parse list-mode data, divide the full acquisition into short scan intervals, and calculate the line-of-response (LOR) midpoint average for each interval. These LOR midpoint averages, known as “radioactivity centroids,” were presumed to represent the center of the radioactivity distribution in the scanner, and it was thought that changes in this metric over time would correspond to intra-scan motion.

Several scans were taken of the 3D Hoffman brain phantom on a GE Discovery IQ PET/CT scanner to test the ability of the radioactivity to indicate intra-scan motion. Each scan incrementally surveyed motion in a different degree of freedom (2 translational and 2 rotational). The radioactivity centroids calculated from these scans correlated linearly to phantom positions/orientations. Centroid measurements over 1-second intervals performed on scans with ~1mCi of activity in the center of the field of view had standard deviations of 0.026 cm in the x- and y-dimensions and 0.020 cm in the z-dimension, which demonstrates high precision and repeatability in this metric. Radioactivity centroids are thus shown to successfully represent discrete motions on the submillimeter scale. It is also shown that while the radioactivity centroid can precisely indicate the amount of motion during an acquisition, it fails to distinguish what type of motion occurred.