The purpose of this study was to assess the efficiency of fluorine-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the characterisation and primary staging of suspicious renal masses, in comparison with computed tomography, the current standard imaging modality. Fifty-three FDG PET studies were performed within the framework of a prospective study: 35 for both characterisation and staging of a suspicious mass, and 18 for staging early after surgical removal of a renal cancer. In the characterisation of renal masses, a high rate of false negative results was observed, leading to a sensitivity, specificity and accuracy of 47%, 80% and 51% respectively, versus 97%, 0/5 and 83% respectively for CT. FDG PET detected all the sites of distant metastasis revealed by CT, as well as eight additional metastatic sites, leading to an accuracy of 94% versus 89% for CT. However, 36/53 patients (68%) did not have any distant metastasis on either CT or on PET. All but one of these patients had a low Fuhrman histological grade and a limited local stage (< or =pT2). We conclude that FDG PET does not offer any advantage over CT for the characterisation of renal masses but that it appears to be an efficient tool for the detection of distant metastasis in renal cancer. However, our data suggest that a selection process could be implemented to determine which patients should undergo PET. FDG PET could be performed in the event of a solitary metastasis or doubtful images on CT. Selection could also be based on adverse histological findings from nephrectomy specimens in order to perform staging early after nephrectomy.

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Imaging the N-methyl-D-aspartate receptors (NMDARs) in the living human brain by positron emission tomography (PET) or single photon emission computed tomography (SPECT) would provide useful information on the role of these receptors in ischemia and in various neurological disorders such as degenerative diseases, epilepsy or schizophrenia. To assess NMDAR radiotracer development and to propose perspectives, we overviewed the PET and SPECT candidate radioligands developed until now. Labelled molecules of interest were classified in three groups according to their binding site: intrachannel pore site blockers, glycine site inhibitors and NR2B selective subunit antagonists.

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This study showed( 18)F-FDG PET to be more sensitive than ( 99m)Tc-depreotide SPECT in the diagnosis of malignancy of SPNs. However, the combination of both techniques may provide additional accuracy.

To investigate the role of the C18 substituents in the agonist/antagonist properties of mineralocorticoids, the activities of certain C18-substituted progesterone (P) derivatives were examined. These compounds were characterized by an unsaturated side-chain in the case of 18-vinylprogesterone (18VP) and 18-ethynylprogesterone (18EP) and by an enone group in the case of 18-oxo-18-vinylprogesterone (18OVP). P and its 18-substituted derivatives bind to the recombinant human MR (hMR) overexpressed in Sf9 cells with the following hierarchy of affinity: P > aldosterone > 18VP > 18EP >> 18OVP. Functional cotransfection assays in CV-1 cells, using mouse mammary tumor virus promoter as a steroid receptor-inducible DNA target sequence, indicated that the mineralocorticoid activity depends on the nature of the C18 substituent. 18VP and 18EP retained the antimineralocorticoid feature of P, with the following order of activity: P = 18VP > 18EP. The antagonist potency of 18VP was higher (IC50, approximately 10(-8) M) than that of spironolactone (IC50, approximately 7 x 10(-8) M), the most widely used aldosterone antagonist. Interestingly, introducing an oxo function at C18 conferred agonist mineralocorticoid properties; 18OVP behaves as a full agonist (ED50, approximately 10(-7) M) with no antagonist activity. In contrast to what was observed when the three 18-substituted P derivatives acted through hMR, they retained the agonist feature of P through the human P receptor, with the following order of potency: P > 18VP = 18OVP > 18EP. The activity of the 18-substituted P derivatives through the human glucocorticoid receptor was only detected at concentrations higher than 10(-6) M; P and 18VP displayed a partial antagonist activity, whereas 18OVP had a full agonist activity (ED50, approximately 2 x 10(-6) M). Thus, the presence of an oxo group at C18(18OVP) does not change the agonist feature of P through human P receptor, but confers to the ligand an agonist activity through hMR, suggesting that the C18 carbonyl group of aldosterone plays a crucial role in its agonist activity.

Efficient and rapid preparations of carbamoyl chlorides and unsymmetrical ureas from tertiary amines and phosgene or its safe equivalent triphosgene [bis(trichloromethyl)carbonate, BTC] are described. First, the reaction of stoichiometric amounts of phosgene with secondary amines was revisited, and it was shown that the formation of carbamoyl chlorides in high yields required careful adjustments of experimental conditions and the use of pyridine as an HCl scavenger. A phosgene-mediated dealkylation of triethylamine was observed when this base was used instead of pyridine. Taking advantage of this observation, a strategy of synthesis of carbamoyl chlorides from tertiary amines and phosgene has been developed. N-Alkyl-N-benzyl(substituted)tetrahydroisoquinolines, -piperazines, -piperidines, or -anilines were treated with stoichiometric amounts of phosgene (or BTC) in CH(2)Cl(2). Tertiary amines bearing electron-enriched benzyl group(s) afforded carbamoyl chlorides in excellent yields and without any contamination by symmetrical ureas. Subsequent additions of primary or secondary amines to these carbamoyl chlorides produced unsymmetrical ureas in single-pot and high-yielding operations. This methodology was applied in (11)C-chemistry. From [(11)C]phosgene, a common precursor used in the preparation of radiotracers for positron emission tomography, a rapid and efficient synthesis of (11)C-carbamoyl chlorides and (11)C-unsymmetrical ureas derived from tetrahydroisoquinoline and piperazine is described. The first example of (11)C-amide formation from the reaction of a (11)C-carbamoyl chloride and an organometallic (cyanocuprate or a Grignard reagent in the presence of a nickel catalyst) is also presented.