Additional file 1: of Quantification of FDG-PET/CT with delayed imaging in patients with newly diagnosed recurrent breast cancer

SUV lesion measures for various subgroups. SUV and MTV for all malignant lesion according to the different subgroups at 1h and 3h, and the change over time. (PDF 232 kb

Structure–Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2<i>S</i>,3<i>R</i>)‑3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid

Herein we describe the first structure–activity relationship study of the broad-range iGluR antagonist (2<i>S</i>,3<i>R</i>)-3-(3-carboxyphenyl)­pyrrolidine-2-carboxylic acid (<b>1</b>) by exploring the pharmacological effect of substituents in the 4, 4′, or 5′ positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4′ position <b>2a</b> which induced a preference in binding affinity for homomeric GluK3 over GluK1 (<i>K</i>_i = 0.87 and 4.8 μM, respectively). Two X-ray structures of ligand binding domains were obtained: <b>2e</b> in GluA2-LBD and <b>2f</b> in GluK1-LBD, both at 1.9 Å resolution. Compound <b>2e</b> induces a D1–D2 domain opening in GluA2-LBD of 17.3–18.8° and <b>2f</b> a domain opening in GluK1-LBD of 17.0–17.5° relative to the structures with glutamate. The pyrrolidine-2-carboxylate moiety of <b>2e</b> and <b>2f</b> shows a similar binding mode as kainate. The 3-carboxyphenyl ring of <b>2e</b> and <b>2f</b> forms contacts comparable to those of the distal carboxylate in kainate