An automated radiosynthesis of 2-[11C]thymidine using anhydrous [11C]urea derived from [11C]phosgene.

2-[11C]Thymidine has been produced from [11C]methane via [11C]phosgene and [11C]urea. Anhydrous [11C]urea was prepared from [11C]phosgene by reaction with liquid ammonia. This novel approach avoids the problems associated with the synthesis of anhydrous [11C]urea from [11C]cyanide. A fully automated system based on a modular approach and under PLC control has been developed. The system provides 2-[11C]thymidine reliably and reproducibly for clinical PET studies. The radiosynthesis takes 45-50 min from [11C]methane and the average yield was 1.5-3.3 GBq (40-90 mCi). The specific radioactivity was typically in the range 29.6-51.8 GBq mumol-1 (0.8-1.4 Ci mumol-1) at EOS corresponding to 6-12 micrograms of stable thymidine. The radiochemical yield of 2-[11C]thymidine was ca. 14% from [11C]methane.

[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand for central 5-HT1A receptors in vitro and in vivo.

[carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is possibly a low-level metabolite appearing in plasma after intravenous administration of [carbonyl-11C]WAY-100635 to human subjects for positron emission tomographic (PET) imaging of brain 5-HT1A receptors. In this study we set out to assess the ability of DWAY to enter brain in vivo and to elucidate its possible interaction with 5-HT1A receptors. Desmethyl-WAY-100635 was labelled efficiently with carbon-11 (t1/2 = 20.4 min) in high specific radioactivity by reaction of its descyclohexanecarbonyl analogue with [carbonyl-11C]cyclohexanecarbonyl chloride. The product was separated in high radiochemical purity by high-performance liquid chromatography (HPLC) and formulated for intravenous injection. Rats were injected intravenously with DWAY, sacrificed at known times and dissected to establish radioactivity content in brain tissues. At 60 min after injection, the ratios of radioactivity concentration in each brain region to that in cerebellum correlated with previous in vitro and in vivo measures of 5-HT1A receptor density. The highest ratio was about 22 in hippocampus. Radioactivity cleared rapidly from plasma; HPLC analysis revealed that DWAY represented 55% of the radioactivity in plasma at 5 min and 33% at 30 min. Only polar radioactive metabolites were detected. Subsequently, a cynomolgus monkey was injected intravenously with DWAY and examined by PET. Maximal whole brain uptake of radioactivity was 5.7% of the administered dose at 5 min after injection. The image acquired between 9 and 90 min showed high radioactivity uptake in brain regions rich in 5-HT1A receptors (e.g. frontal cortex and neocortex), moderate uptake in raphe nuclei and low uptake in cerebellum. A transient equilibrium was achieved in cortical regions at about 60 min, when the ratio of radioactivity concentration in frontal cortex to that in cerebellum reached 6. The corresponding ratio for raphe nuclei was about 3. Radioactive metabolites appeared rapidly in plasma, but these were all more polar than DWAY, which represented 52% of the radioactivity in plasma at 4 min and 20% at 55 min. In a second PET experiment, in which a cynomolgus monkey was pretreated with the selective 5-HT1A receptor antagonist, WAY-100635, at 25 min before DWAY injection, radioactivity in all brain regions was reduced to that in cerebellum. Autoradiography of post mortem human brain cryosections after incubation with DWAY successfully delineated 5-HT1A receptor distribution. Receptor-specific binding was eliminated in the presence of the selective 5-HT1A receptor agonist, 8-OH-DPAT [(+/-)-8-hydroxy-2-dipropylaminotetralin]. These findings show that: (a) intravenously administered DWAY is well able to penetrate brain in rat and monkey, (b) DWAY is a highly effective radioligand for brain 5-HT1A receptors in rat and monkey in vivo and for human brain in vitro, and (c) the metabolism and kinetics of DWAY appear favourable to successful biomathematical modelling of acquired PET data. Thus, DWAY warrants further evaluation as a radioligand for PET studies of 5-HT1A receptors in human brain.

Surgical plating of a fractured radius and ulna in a wild Canada lynx.

A free-ranging, adult male Canada-lynx (Lynx canadensis) experienced a closed, complete, non-comminuted transverse fracture of the left radius and ulna when captured in a leg snare. A dynamic compression plate (DCP) attached to the anterior surface of the radius was used to stabilize the fracture. Radiographs 44 days post-surgery indicated advanced primary bone healing. The lynx was released 46 days post-surgery near the site of capture. Radiotelemetry indicated long-term survival and movements similar to other males monitored during the same period.

Organochlorine and heavy metal contaminants in wild mink in western Northwest Territories, Canada.

The mink (Mustela vision) is a top trophic level species that readily bioaccumulates environmental pollutants and is considered to be a sensitive indicator of ecosystem health. Spatial trends in levels of organochlorine and heavy metal contaminant burdens were determined from 1991 to 1995 for wild mink from western Northwest Territories (NWT), Canada. Tissue samples from 207 mink from seven communities were analyzed for residues of 63 organochlorines and 10 heavy metals. All groups of organochlorines were detected in mink livers at relatively low levels; maximum community means were 9.52 ng/g sigma DDT and 73.07 ng/g sigma PCB (sum of 43 congeners). There was a general trend of decreasing organochlorine burdens along a northerly or westerly gradient for some groups of compounds, primarily sigma DDT, sigma PCB, sigma chlordane and dieldrin. Toxic equivalents (TEQs) of mink liver tissue were low, with the maximum community mean of 0.28 pg/g wet weight (5.5 pg/g lipid weight). Levels of heavy metal burdens in liver and kidney tissues were found to be relatively low, with the exception of Hg, which was found at moderate levels. There was no obvious geographic trend to the pattern of heavy metal burdens. The available evidence suggests that long-range atmospheric transport is the main source of the organochlorine contaminants observed. Local conditions (geology, water and soil chemistry, diet, etc.) may determine heavy metal burdens. Levels of contaminants in NWT mink appear to be one to two orders of magnitude lower than levels observed to cause reproductive impairment, reduced survival of kits, or lethality in adult mink. In the western NWT mink may be the best indicator to assess trends in environmental contaminants and ecosystem health; periodic monitoring is recommended.

Current trends in obstetric and gynecologic academic faculty manpower.

Five prior academic manpower studies were completed by ACOG and the Association of Professors of Gynecology and Obstetrics in 1977-1990. In the current survey, a similar questionnaire was sent to the 130 accredited medical school departments of obstetrics-gynecology; 127 responded. The mean number of full-time faculty members per department is 25.8, an increase of 14% over the last 4 years. Among faculty, women constitute 30.4%, an increase of five percentage points since 1990. Certified subspecialists on faculties have increased 27% in the last 4 years, but decreasing percentages of all subspecialists are in faculty positions compared with private practice settings. Chairmen remain optimistic about continued faculty growth despite the inroads of managed care.

Propionyl-L-carnitine: labelling in the N-methyl position with carbon-11 and pharmacokinetic studies in rats.

The prospective therapeutic, propionyl-L-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t1/2 = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-L-carnitine hydrochloride with no-carrier-added [11C]iodomethane (produced from cyclotron-produced [11C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl-11C]propionyl-L-carnitine in 62% radiochemical yield (decay-corrected from [11C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl-11C]Propionyl-L-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl-11C]L-carnitine and [N-methyl-11C]acetyl-L-carnitine.

Environmental contaminants in wild mink in the Northwest Territories, Canada.

As a top trophic level species that readily bioaccumulates environmental pollutants, the mink (Mustela vison) is considered to be a sensitive indicator of ecosystem health. Here we report on the first 2 years of a 4-year program established to examine organochlorine and heavy metal residues in wild mink from western Northwest Territories (NWT), Canada. Tissue samples taken from up to 24 mink harvested from each of five sites in 1991-92 and 1992-93 were analyzed for residues of a suite of 63 organochlorines in fat and liver samples, including 43 polychlorinated biphenyl (PCB) congeners and 20 pesticides, and residues of 10 heavy metals in liver and kidney samples. Overall, contaminant levels were low in comparison with levels in other mink studied in North America. Sigma PCB residues (sum of 43 congeners) ranged from a mean of 5.32 ng/g wet weight in the livers of Inuvik mink (the most northerly collection site) to 27.67 ng/g in mink from Fort Smith (the most southerly collection site). There appeared to be no differences in organochlorine burden between sexes. Heavy metal residues were also comparatively low, with the exception of total mercury, which was at moderate levels (community means of 1.16-3.30 micrograms/g wet wt. in liver samples). There was a distinct trend of decreasing organochlorine contaminant burdens with increasing latitude, but no trend in heavy metal burdens was evident. There was a doubling of mean sigma PCB levels in Inuvik mink from 5.32 ng/g wet weight in 1991-92 to 10.69 ng/g in 1992-93. Population indices derived from age and sex ratios of the harvest, coupled with comparatively low levels of contaminants, suggest little or no effects on mink reproduction or population health as a result of these contaminants. Long-range atmospheric transport is probably the major source of most of the contaminants. Additional collections will further elucidate spatial and temporal trends in contaminant levels in NWT mink.