PET radiotracer development for imaging high-affinity state of dopamine D2 and D3 receptors: Binding studies of fluorine-18 labeled aminotetralins in rodents.

Imaging the high-affinity, functional state (HA) of dopamine D2 and D3 receptors has been pursued in PET imaging studies of various brain functions. We report further evaluation of 18 F-5-OH-FPPAT, and the newer 18 F-5-OH-FHXPAT and 18 F-7-OH-FHXPAT. Syntheses of 18 F-5-OH-FHXPAT and 18 F-7-OH-FHXPAT were improved by modifications of our previously reported procedures. Brain slices and brain homogenates from male Sprague-Dawley rats were used with the 3 radiotracers (74-111 kBq/cc). Competition with dopamine (1-100 nM) and Gpp(NH)p (10-50 µM) were carried out to demonstrate binding to dopamine D2 and D3 HA-states and binding kinetics of 18 F-5-OH-FPPAT measured. Ex vivo brain slice autoradiography was carried out on rats administered with 18 F-5-OH-FHXPAT to ascertain HA-state binding. PET/CT imaging in rats and wild type (WT) and D2 knock-out mice were carried out using 18 F-7-OH-FHXPAT (2-37 MBq). Striatum was clearly visualized by the three radiotracers in brain slices and dopamine displaced more than 80% of binding, with dissociation rate in homogenates of 2.2 × 10-2 min-1 for 18 F-5-OH-FPPAT. Treatment with Gpp(NH)p significantly reduced 50-80% striatal binding with faster dissociation rates (5.0 × 10-2 min-1 ), suggesting HA-state binding of 18 F-5-OH-FPPAT and 18 F-5-OH-FHXPAT. Striatal binding of 18 F-5-OH-FHXPAT in ex vivo brain slices were sensitive to Gpp(NH)p, suggesting HA-state binding in vivo. PET binding ratios of 18 F-7-OH-FHXPAT in rat brain were ventral striatum/cerebellum = 2.09 and dorsal striatum/cerebellum = 1.65; similar binding ratios were found in the D2 WT mice. These results suggest that in vivo PET measures of agonists in the brain at least in part reflect binding to the membrane-bound HA-state of the dopamine receptor.

Kenaf fibre treatment and its impact on the static, dynamic, hydrophobicity and barrier properties of sustainable polystyrene biocomposites.

Natural fibre-polymer adhesion can be improved by treating the fibre surface or polymer. In this study, resorcinol-hexamethylenetetramine mixture (R-HMT) is used as a chemical treatment for kenaf fibre waste to extend the interfacial adhesion between the fibre-polystyrene matrices. The effect of the untreated and treated kenaf fibre (designated as UK and TK fibre) on the thermal (DSC), viscoelastic, mechanical, hydrophobicity, and barrier properties of polystyrene (PS) was studied. Four different percentages of each type of fibre (10, 20, 30, and 40 wt%) were used. The chemical structure of the TK fibre was confirmed by Fourier-transform infrared spectroscopy (FT-IR) analysis. The compatibility of the fibre-polymer was investigated by scanning electron microscopy (SEM). The results showed that the use of the treated fibre at 30 wt%, enhanced the tensile strength by 148% and 212% compared to neat PS and PS/UK-30, respectively, indicating a good fibre bond adhesion. The DMA data demonstrated that the storage modulus increased significantly, especially for the PS/TK-30 composite. Meanwhile, the glass transition temperature (T g) shifted to a lower temperature for both types of fibre. Also, the hydrophobicity of the PS composites, which was determined by thickness swelling measurements, was improved when the TK fibre was inserted. Furthermore, water vapor and oxygen transmission rates were determined. A good correlation between most of the properties for the PS composite-based treated fibre was observed, which revealed the possibility of using these materials for sustainable automotive components and gas sensitive packaging applications.