Comparison of 68Ga-DOTANOC with 18F-FDG using PET/MRI imaging in patients with pulmonary tuberculosis

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax[FDG] for parenchymal lesions was 7.69 (range 3.00–15.88); median SUVmax[DOTANOC] was 2.59 (1.48–6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax[FDG] 4.17–6.18; SUVmax[DOTANOC] 2.92–4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed

Estrogen-dependent regulation of sodium/hydrogen exchanger-3 (NHE3) expression via estrogen receptor β in proximal colon of pregnant mice

Although constipation is very common during pregnancy, the exact mechanism is unknown. We hypothesized that the involvement of estrogen receptor (ER) in the regulation of electrolyte transporter in the colon leads to constipation. In this study, the intestines of normal female ICR mouse and pregnant mice were examined for the expression of ERβ and ERβ by immunohistochemistry and in situ hybridization. ERα, but not ERα, was expressed in surface epithelial cells of the proximal, but not distal, colon on pregnancy days 10, 15, and 18, but not day 5, and the number of ERα-positive cells increased signiWcantly during pregnancy. Expression of NHE3, the gene that harbors estrogen response element, examined by immunohistochemistry and western blotting, was localized in the surface epithelial cells of the proximal colon and increased in parallel with ERβ expression. In ovariectomized mice, NHE3 expression was only marginal and was up-regulated after treatment with 17- estradiol (E2), but not E 2 + ICI 182,780 (estrogen receptor antagonist). Moreover, knock-down of ERβ expression by electroporetically transfected siRNA resulted in a signiWcant reduction of NHE3 expression. These results indicate that ERβ regulates the expression of NHE3 in the proximal colon of pregnant mice through estrogen action, suggesting the involvement of increased sodium absorption by up-regulated NHE3 in constipation during pregnancy