The effect of vehicle on the tissue distribution profiles of radioiodinated cholesterol esters in the rat

Several groups have examined the possible use of radioiodinated cholesterol esters to achieve selective uptake of radioactivity in the adrenal cortex and have obtained variable results. This study indicates that the tissue distribution profile varies not only with the type of ester, but also with the vehicle employed for administration. Radioiodinated 19-iodocholesteryl (125-IC), iodocholesteryl palmitate (125-ICP)and iodocholesteryl oleate (125-ICO) were dissolved in either tween vehicle (saline containing 1.6% tween 80 and 10% ethanol) or myristate vehicle (isopropyl myristate-ethanol, 1:5 v/v) and administered i.v. to rats. Irrespective of the agent, considerably more radioactivity appeared in the target organs when the tween vehicle was employed. When the myristate vehicle was used, higher levels of radioactivity appeared in the lung. This finding suggests precipitation of the agents from the myristate vehicle occurred upon administration. In the tween vehicle, 125-ICO showed almost three times greater predilection for adrenal cortex than 125-ICP with levels of activity approaching those seen for 125-IC. Adrenal activity and adrenal to non-target ratios were sufficient for visualization of the adrenals at 5 days after injection of 125-ICO in the tween vehicle. Lipid extraction and TLC analysis of tissue radioactivity revealed that radioactivity in the adrenal and ovary was predominantly in an esterified form. Further analysis of the esters present after injection of 125-ICP showed these to be a mixture of mono and polyunsaturated esters. The site of hydrolysis and subsequent reesterification is an interesting biochemical aspect that remains to be elucidated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24488/1/0000764.pd

Changes in the Frontotemporal Cortex and Cognitive Correlates in First-Episode Psychosis

Background: Loss of cortical volume in frontotemporal regions has been reported in patients with schizophrenia and their relatives. Cortical area and thickness are determined by different genetic processes, and measuring these parameters separately may clarify disturbances in corticogenesis relevant to schizophrenia. Our study also explored clinical and cognitive correlates of these parameters.Methods: Thirty-seven patients with first-episode psychosis (34 schizophrenia, 3 schizoaffective disorder) and 38 healthy control subjects matched for age and sex took part in the study. Imaging was performed on an magnetic resonance imaging 1.5-T scanner. Area and thickness of the frontotemporal cortex were measured using a surface-based morphometry method (Freesurfer). All subjects underwent neuropsychologic testing that included measures of premorbid and current IQ, working and verbal memory, and executive function.Results: Reductions in cortical area, more marked in the temporal cortex, were present in patients. Overall frontotemporal cortical thickness did not differ between groups, although regional thinning of the right superior temporal region was observed in patients. There was a significant association of both premorbid IQ and IQ at disease onset with area, but not thickness, of the frontotemporal cortex, and working memory span was associated with area of the frontal cortex. These associations remained significant when only patients with schizophrenia were considered.Conclusions: Our results suggest an early disruption of corticogenesis in schizophrenia, although the effect of subsequent environmental factors cannot be excluded. In addition, cortical abnormalities are subject to regional variations and differ from those present in neurodegenerative diseases

Potential tumor or organ imaging agents--31. Radioiodinated sterol benzoates and carbamates

A series of radioiodinated benzoate and carbamate esters of cholesterol and pregnenolone wherein the acyl moiety served as the carrier for radioiodine was synthesized and evaluated as potential imaging agents for the adrenal cortex. 2,6-Dimethyl-3-iodobenzoyl and N-(4-iodophenyl) carbamoyl groups were chosen as the acyl functionality in an attempt to provide esters resistant to in vivo hydrolysis. Tissue disposition studies in rats revealed that their biodistribution was determined by the attached sterol carrier--the cholesterol esters demonstrated significant uptake at 24 h in the adrenal whereas the corresponding pregnenolone derivatives showed only slight affinity for steroid-secreting tissues at this time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28212/1/0000665.pd

Synthesis of 11C-labelled thymidine for tumor visualization using positron emission tomography

A no-carrier added synthesis of [11C]thymidine from cyclotron produced [11C]methyl iodide is presented. The bis-silylated derivative of the lithium salt of 5-bromo-2'-deoxyuridine is treated with [11C]methyl iodide in THF at -50[deg]C giving 20-30 mCi [11C]thymidine in a 40-70% radiochemical yield. Purification is performed by reversed phase chromatography on a C18 column. The whole procedure takes 25 min and the specific activity is about 20-30 mCi/[mu]mol at the end of the synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28118/1/0000567.pd