Microbial volatile organic compounds--what substances can be found in sick buildings?

There is a relationship between damp buildings and health complaints. Damp conditions in building constructions also favour the growth of micro-organisms. Growth of micro-organisms results in the production of volatile organic compounds, which has been shown to have an impact on Indoor-air monitored via a microbial volatile organic compound (MVOC) analysis. In order to widen the applicability of MVOC analysis, it is necessary to increase this analysis by including more volatiles. By active sampling on Anasorb 747 and selected ion monitoring on a mass spectrometer equipped with a quadropole detector, it is possible to determine these volatiles with sufficient accuracy in indoor air of non-industrial buildings.

Positron emission tomography shows high specific uptake of racemic carbon-11 labelled norepinephrine in the primate heart.

(-)-Norepinephrine is the predominant neurotransmitter of the sympathetic innervation of the heart. Racemic norepinephrine was labelled with carbon-11 and injected i.v. into Cynomolgus monkeys. Five minutes after injection there was a more than tenfold higher radioactivity in the heart than in adjacent tissue. Pretreatment with the norepinephrine reuptake inhibitor desipramine reduced the uptake by more than 80%. The high specific uptake of racemic [11C]norepinephrine indicates that enantiomerically pure (-)-[11C]norepinephrine has promising potential for detailed mapping of the sympathetic innervation of the human myocardium.

Selective synthesis of racemic 1-11C-labelled norepinephrine, octopamine, norphenylephrine and phenylethanolamine using [11C]nitromethane.

A new and simple method for the selective condensation of no-carrier-added [11C]nitromethane (1) with various substituted (protected) benzaldehydes to [beta-11C]beta-nitrophenethyl alcohols was developed. This method which utilizes tetrabutylammonium fluoride in THF as a catalyst gave a condensation yield of 80-90% and a selectivity of 80-90% for [11C]nitroalcohol vs [11C]nitrostyrene formation within 2 min. Reduction of these [11C]nitroalcohols with Raney nickel in formic acid gave the corresponding [11C]aminoalcohols in a yield of 60-90%. Boron tribromide was used for the cleavage of 4-methoxy and 3,4-(methylenedioxy) phenol protecting groups. After HPLC-purification, racemic 1-11C-labelled norepinephrine (7), phenylethanolamine (4), norphenylephrine (5) and octopamine (6) were prepared in a 12-30% decay corrected total radiochemical yield (20-50% counted from 1) with an overall synthesis time of 40-70 min from end of bombardment (EOB). The radiochemical purity was > 98% and the specific radioactivity 700-1500 Ci/mmol (26-56 GBq/mumol).

Preparation of [1-11C]dopamine, [1-11C]p-tyramine and [1-11C]m-tyramine. Autoradiography and PET examination of [1-11C]dopamine in primates.

A method for no-carrier-added 1-11C-labelling of 3-hydroxy-, 4-hydroxy- and 3,4-dihydroxy-substituted phenethylamines is described. [11C]Dopamine, [11C]p-tyramine and [11C]m-tyramine were prepared from on-line produced [11C]nitromethane. Condensation of [11C]nitromethane with various protected and unprotected benzaldehydes was investigated. A one-pot two-step reduction of the substituted 11C-labelled nitrostyrene intermediates, gave after hydrolysis and reversed-phase semi-preparative HPLC-purification the corresponding labelled amines in a total radiochemical yield of 8-20% (based on [11C]CO2 and decay-corrected). The total synthesis time was 45-50 min with a specific radioactivity of 400-1000 Ci/mmol (15-37 GBq/mumol). The radiochemical purity was higher than 98% [11C]Dopamine was used for in vitro autoradiography on human post-mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. Autoradiographic examination of [11C]dopamine binding on human brain section post-mortem demonstrated specific binding in the caudate putamen and the substantia nigra, regions with a dense dopaminergic innervation. Some binding was also seen in the globus pallidum, nucleus ventralis of the thalamus and in nucleus dentatus of the cerebellum, regions where the dopaminergic innervation is very low. In PET examinations of [11C]dopamine binding in Cynomolgus monkeys there was a high uptake of radioactivity in the pituitary, the kidneys and the heart. Any passage of [11C]dopamine across the blood-brain barrier could not be demonstrated. In human PET studies [11C]dopamine has potential as a radioligand for examination of the myocardium, pituitary and kidneys.

Synthesis of [1-11C]D-glucose and [1-11C]D-mannose from on-line produced [11C]nitromethane.

A method for the preparation of [1-11C]D-glucose (III) and [1-11C] D-mannose (IV) from [11C] nitromethane is described. [11C]Nitromethane was produced using the on-line method from [11C]methyl iodide. The condensation of no-carrier-added or carrier-added [11C]nitromethane with D-arabinose to form the intermediate epimeric [1-11C]D-nitro alcohols (I and II) was investigated under various conditions. Compounds I and II were converted to III and IV by the classical Nef reaction with IV as the major product [(IV)/(III) = 3/1-4/1]. The isolated radiochemical yield of III and IV was 25-30% (based on [11C]nitromethane and decay-corrected) and 14-17% (EOB) with a total synthesis time of 50 min, including HPLC-purification. Compounds III and IV were isolated using semi-preparative HPLC and the radiochemical purity was greater than 97%. In a typical run, 1.5-2.0 mCi of III and 6-8 mCi of IV could be isolated (starting from 70-90 mCi [11C]nitromethane).

On-line synthesis of [11C]nitroalkanes.

The on-line synthesis of 1-11C-labelled nitroalkanes [nitromethane (I), nitroethane (II) and nitropropane (III)], from their corresponding 1-11C-labelled alkyl iodides, by use of a heated silver nitrite column is described. The radiochemical yields of I, II and III were of the order of 40-70%, based on the corresponding [1-11C]alkyl iodides. The total radiochemical yields, starting from [11C]carbon dioxide, were of the order of 25-55% with an overall synthesis time of 8-15 min.

In vivo and in vitro receptor autoradiography of the human brain using an 11C-labelled benzodiazepine analogue.

In vitro autoradiography of an 11C-labelled ligand, Ro 15-1788, has been used to visualize benzodiazepine binding sites in large human brain cryo-sections. In parallel, using the same radioligand, an in vivo study of a human healthy volunteer was performed, by means of positron emission tomography (PET). The in vitro and in vivo mapping of the ligand demonstrated a very similar binding pattern, although the poor resolution of PET precluded a full discrimination of fine details. The 11C-autoradiograms showed good spatial resolution, even with distinction of different layers in the cerebral and cerebellar cortex. In a separate experiment, the spatial resolution of 11C-autoradiography was found to be 180 microns, using 80-microns-thick cryo-sections. It is emphasized that in vitro and in vivo studies of the same radioligand give complementary information, which is valuable in the assessment of PET images.

The Bücherer-Strecker synthesis of D- and L-(1-11C)tyrosine and the in vivo study of L-(1-11C)tyrosine in human brain using positron emission tomography.

The synthesis of D- and L-(1-11C)tyrosine, starting with 11C-cyanide, is reported. DL-(1-11C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added 11C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure D- and L-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of 11C-cyanide, with a radiochemical yield of D- and L-amino acid of 40%-60%. The D- and L-(1-11C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3-0.5 Ci/mmol and a radiochemical purity better than 99%. The 11C labelled L-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).