I-PET score: Combining whole body iodine and 18 F-FDG PET/CT imaging to predict progression in structurally or biochemically incomplete thyroid cancer.

OBJECTIVE: We propose a new scoring system (I-PET) combining whole body scan (WBS) and FDG findings to identify patients who have or are likely to become refractory to radioactive iodine. DESIGN: Retrospective analysis of 142 patients age >18 with differentiated thyroid cancer who had a F-18 labelled fluoro-2-deoxyglucose (18 F-FDG) positron emission tomography (PET) and WBS within a 6-month period between 2010 and 2020. Pairs of 18 F-FDG PET and WBS were reviewed by three independent nuclear medicine physicians and an I-PET score was assigned: I-PET [0]: Iodine -ve/FDG -ve, I-PET [1]: Iodine +ve/FDG -ve, I-PET [2]: Iodine +ve/FDG +ve and I-PET [3]: Iodine -ve/FDG +ve. Patients with FDG +ve lesions (I-PET [2] and I-PET [3]) were further classified into groups A and B if SUVmax was ≤5 or >5, respectively. Follow-up data were obtained by chart review. Progression was defined as structural progression as per RECIST 1.1 or further surgical intervention; or biochemical progression as unstimulated thyroglobulin increasing >20% from baseline. RESULTS: Of 142 patients included in the study 121 patients had follow-up data available for review. At baseline, 49 patients were classified as I-PET [0], 10 as I-PET [1], 16 as I-PET [2] and 46 as I-PET [3]. Progression was seen in 11/49 (22%) of I-PET [0], 4/10 (40%) of I-PET [1], 10/16 (63%) of I-PET [2] and 34/46 (74%) of I-PET [3] (p < 0.001). I-PET [2B] and I-PET [3B] had a progression rate of 88% (7/8) and 78% (25/32), respectively. I-PET [3B] were 9.6 times more likely to commence multikinase inhibitor therapy (p = 0.001) and had 8 times greater mortality (p = 0.003) than patients in other I-PET groups combined. CONCLUSION: I-PET is a simple readily acquired imaging biomarker that potentially enhances the dynamic risk stratification and guide treatment in thyroid cancer.

Case Report of 18F-FDG PET/CT Features of Polyacrylamide Hydrogel Mammoplasty.

ABSTRACT: A 57-year-old woman with a history of previous bilateral breast polyacrylamide hydrogel injection presented for 18F-FDG PET/CT imaging to investigate recurrent retroperitoneal liposarcoma. Incidental symmetrical FDG-positive accumulation was noted in the bilateral axillae tracking between the interpectoral planes. The finding is consistent with a chronic inflammatory process secondary to the migration of the polyacrylamide hydrogel injections.

Catalase-Like Antioxidant Activity is Unaltered in Hypochlorous Acid Oxidized Horse Heart Myoglobin.

Activated neutrophils release myeloperoxidase that produces the potent oxidant hypochlorous acid (HOCl). Exposure of the oxygen transport protein horse heart myoglobin (hhMb) to HOCl inhibits Iron III (Fe(III))-heme reduction by cytochrome b5 to oxygen-binding Iron II (Fe(II))Mb. Pathological concentrations of HOCl yielded myoglobin oxidation products of increased electrophoretic mobility and markedly different UV/Vis absorbance. Mass analysis indicated HOCl caused successive mass increases of 16 a.m.u., consistent serial addition of molecular oxygen to the protein. By contrast, parallel analysis of protein chlorination by quantitative mass spectrometry revealed a comparatively minor increase in the 3-chlorotyrosine/tyrosine ratio. Pre-treatment of hhMb with HOCl affected the peroxidase reaction between the hemoprotein and H2O2 as judged by a HOCl dose-dependent decrease in spin-trapped tyrosyl radical detected by electron paramagnetic resonance (EPR) spectroscopy and the rate constant of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) oxidation. By contrast, Mb catalase-like antioxidant activity remained unchanged under the same conditions. Notably, HOCl-modification of Mb decreased the rate of ferric-to-ferrous Mb reduction by a cytochrome b5 reductase system. Taken together, these data indicate oxidizing HOCl promotes Mb oxidation but not chlorination and that oxidized Mb shows altered Mb peroxidase-like activity and diminished rates of one-electron reduction by cytochrome b5 reductase, possibly affecting oxygen storage and transport however, Mb-catalase-like antioxidant activity remains unchanged.

Correction to: Selenite-mediated production of superoxide radical anions in A549 cancer cells is accompanied by a selective increase in SOD1 concentration, enhanced apoptosis and Se-Cu bonding.

In the original article there were errors in the methods section. Thus, within Table 1: (i) the primer sequence pair for SOD-2 was incorrectly cited; (ii) the primer sequence pair used for SOD 1 was incorrect and did not target the gene of interest. Additional experiments were performed with correctly designed SOD1 primer pair and the outcomes documented here.

Selenite-mediated production of superoxide radical anions in A549 cancer cells is accompanied by a selective increase in SOD1 concentration, enhanced apoptosis and Se-Cu bonding.

Selenite may exert its cytotoxic effects against cancer cells via the generation of reactive oxygen species (ROS). We investigated sources of, and the cellular response to, superoxide radical anion (O2 (·-)) generated in human A549 lung cancer cells after treatment with selenite. A temporal delay was observed between selenite treatment and increases in O2 (·-) production and biomarkers of apoptosis/necrosis, indicating that the reduction of selenite by the glutathione reductase/NADPH system (yielding O2 (·-)) is a minor contributor to ROS production under these conditions. By contrast, mitochondrial and NADPH oxidase O2 (·-) generation were the major contributors. Treatment with a ROS scavenger [poly(ethylene glycol)-conjugated superoxide dismutase (SOD) or sodium 4,5-dihydroxybenzene-1,3-disulfonate] 20 h after the initial selenite treatment inhibited both ROS generation and apoptosis determined at 24 h. In addition, SOD1 was selectively upregulated and its perinuclear cytoplasmic distribution was colocalised with the cellular distribution of selenium. Interestingly, messenger RNA for manganese superoxide dismutase, catalase, inducible haem oxygenase 1 and glutathione peroxidase either remained unchanged or showed a delayed response to selenite treatment. Colocalisation of Cu and Se in these cells (Weekley et al. in J. Am. Chem. Soc. 133:18272-18279, 2011) potentially results from the formation of a Cu-Se species, as indicated by Cu K-edge extended X-ray absorption fine structure spectra. Overall, SOD1 is upregulated in response to selenite-mediated ROS generation, and this likely leads to an accumulation of toxic hydrogen peroxide that is temporally related to decreased cancer cell viability. Increased expression of SOD1 gene/protein coupled with formation of a Cu-Se species may explain the colocalisation of Cu and Se observed in these cells.