Molecular imaging of liver inflammation using an anti-VCAM-1 nanobody.

To date, a biopsy is mandatory to evaluate parenchymal inflammation in the liver. Here, we evaluated whether molecular imaging of vascular cell adhesion molecule-1 (VCAM-1) could be used as an alternative non-invasive tool to detect liver inflammation in the setting of chronic liver disease. To do so, we radiolabeled anti-VCAM-1 nanobody (99mTc-cAbVCAM1-5) and used single-photon emission computed tomography (SPECT) to quantify liver uptake in preclinical models of non-alcoholic fatty liver disease (NAFLD) with various degree of liver inflammation: wild-type mice fed a normal or high-fat diet (HFD), FOZ fed a HFD and C57BL6/J fed a choline-deficient or -supplemented HFD. 99mTc-cAbVCAM1-5 uptake strongly correlates with liver histological inflammatory score and with molecular inflammatory markers. The diagnostic power to detect any degree of liver inflammation is excellent (AUROC 0.85-0.99). These data build the rationale to investigate 99mTc-cAbVCAM1-5 imaging to detect liver inflammation in patients with NAFLD, a largely unmet medical need.

Preclinical characterization of a novel radiolabeled analog of practolol for the molecular imaging of myocardial ß-adrenoceptor density.

BACKGROUND: The great clinical potential of myocardial ß-AR imaging has been shown by recent studies evaluating the ß-AR-specific, non-selective agent [(11)C]-CGP12177 in the setting of idiopathic-dilated cardiomyopathy, and myocardial infarction. However, the short half-life of (11)C hampers the potential of [(11)C]-CGP12177 for routine clinical use. AMI9 is an analog of the ß-adrenoceptor ligand practolol that can readily be labeled using radioactive isotopes of iodine. The present study was aimed at characterizing the in vitro, ex vivo, and in vivo ß-AR binding properties of [(125)I]-AMI9. METHODS AND RESULTS: Newborn rat cardiomyocytes were used for saturation and kinetic binding assays as well as for displacement and competition experiments. Isolated perfused rat hearts were used to evaluate the pharmacological activity of AMI9. The in vivo kinetics of [(125)I]-AMI9 were studied using biodistribution experiments in mice. [1(25)I]-AMI9 displayed high specific affinity for ß-AR with no ß-AR subtype selectivity (K D, 5.6 ± 0.3 nM; B max, 231 ± 7 fmol·(mg protein)(-1)). AMI9 potently inhibited the inotropic effects of isoproterenol. The early in vivo cardiac and lung activities of [(125)I]-AMI9 compared favorably with those of the clinically validated tracer CGP12177. CONCLUSION: Iodine-labeled AMI9 is a promising agent for the molecular imaging of myocardial ß-AR density.

Uranium speciation in drinking water from drilled wells in southern Finland and its potential links to health effects.

Exceptionally high concentrations of natural uranium have been found in drinking water originating from drilled wells in Southern Finland. However, no clear clinical symptoms have been observed among the exposed population. Hence a question arose as to whether uranium speciation could be one reason for the lack of significant adverse health effects. Uranium species were determined using time-resolved laser-induced fluorescence spectroscopy. We performed multi-element chemical analyses in these water samples, and predictive calculations were carried out using up-to-date thermodynamic data. The results indicated good agreement between measurements and modeling. The low toxicity of Finnish bedrockwater may be due to the predominance of two calcium-dependent species, Ca2UO2(CO3)3(aq) and CaUO2(CO3)3(2-), whose nontoxicity for cells has been described previously. This interdisciplinary study describes chemical speciation of drinking water with elevated uranium concentrations and the potential consequence on health. From these results, it appears that modeling could be used for a better understanding of uranium toxicity of drinking water in the event of contamination.