Diagnostic value of 18F-FDG-PET/CT for the follow-up and restaging of soft tissue sarcomas in adults.

PURPOSE: The purpose of this study was to evaluate the clinical utility of 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG-PET/CT) in the follow-up of adult patients with soft tissue sarcomas. MATERIALS AND METHODS: We prospectively evaluated 37 consecutive patients with known soft tissue sarcoma with 18F-FDG-PET/CT examination for suspected recurrence of disease. They were 21 men and 16 women with a mean age of 49.6±10.6 (SD) years (range, 34-75years). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18F-FDG-PET/CT examination were calculated on a per patient basis. RESULTS: 18F-FDG-PET/CT showed an overall diagnostic accuracy of 91.8%, sensitivity of 90% and a specificity of 100%. The positive predictive value and negative predictive value were 100 and 70%, respectively. The 18F-FDG-PET/CT interpretations were correct in 34/37 patients (91.8%). Incorrect interpretations occurred in three patients (8.1%). Reasons for false negative findings were low 18F-FDG uptake of local recurrence in one patient and low 18F-FDG uptake of subcentimetric inguinal lymph node metastases. CONCLUSION: 18F-FDG-PET/CT has a high diagnostic value in the follow-up of patients with soft tissue sarcoma.

Synthesis of new antioxidant conjugates and their in vitro hydrolysis with Stratum corneum enzymes.

The aim of this study was to synthesize new precursors, combinations of well-known antioxidant molecules: resveratrol, lipoic acid and vitamin E to improve their photo-stability and to modulate their lipophylic character. Active antioxidants are available through a controlled release by the action of skin enzymes upon a topic application. Two conjugates are described, the combinations of resveratrol-lipoic acid (6) and resveratrol-vitamin E (10). Both compounds are new molecules. This work describes their synthesis, characterization, stability study and in vitro biohydrolysis. Stratum corneum enzymes efficiently hydrolysed in vitro precursor 6 and liberate both active molecules, resveratrol and lipoic acid over the period of 72 h. Precursor 10 was hydrolysed in vitro by combination of Stratum corneum enzymes and the cholesterol esterase. A simple technique of preparation of the human Stratum corneum hydrolases is also described.

Full stereochemical understanding in a new (2R,3R,4R)-4-hydroxyisoleucine synthesis.

We present the crystal and molecular structures of 2,3,6,7,8,8a-hexahydro-6,8-methano-7,7,8a-trimethyl-3-(1-methyl-2-oxopropylidene)-5H-1,4-benzoxazin-2-one, C16H21NO3, (III), and 2,3,6,7,8,8a-hexahydro-3-(2-hydroxy-1-methylpropyl)-6,8-methano-7,7,8a-trimethyl-5H-1,4-benzoxazin-2-one, C16H25NO3, (V). These compounds are two of the four key intermediates in our synthetic route to (2R,3R,4R)-4-hydroxyisoleucine. The two structures provide a full understanding of the stereochemistry in successive steps. This synthesis was based on a new optically pure chiral oxazinone auxiliary derived from (1R,2R,5R)-2-hydroxypinan-3-one.

S-Acyl-2-thioethyl aryl phosphotriester derivatives as mononucleotide prodrugs.

The synthesis and biological activities of phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a phenyl group or L-tyrosinyl residues are reported. The target compounds were obtained via either P(V) or P(III) chemistry from the appropriate aryl precursors. All the derivatives were evaluated for their in vitro anti-HIV activity, and they appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments, with EC(50) values between the micro- and nanomolar range. Furthermore, compounds incorporating an amino- and/or acid-substituted tyrosinyl residue demonstrated significant anti-HIV effects in thymidine kinase-deficient (TK(-)) cells showing their ability to act as mononucleotide prodrugs. The proposed decomposition process of these mixed mononucleoside aryl phosphotriesters may involve esterase activation followed by phosphodiesterase hydrolysis.

Two key chiral intermediates in a new 4-hydroxyisoleucine synthesis.

We present the crystal and molecular structure of two key compounds of a new synthesis strategy for isomers of natural (2S,3R, 4S)-4-hydroxyisoleucines, 2,3,5,6,7, 8-hexahydro-3-(1-hydroxy-1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a-trimethyl-5H-1,4-benzoxazin-2-one, C(16)H(23)NO(4), and 2,3,5,6,7, 8-hexahydro-3-(1-methyl-2-oxopropyl)-6,8-methano-7,7, 8a-trimethyl-5H-1,4-benzoxazin-2-one, C(16)H(23)NO(3). A new optically pure chiral oxazinone auxiliary derived from (1R,2R, 5R)-2-hydroxypinan-3-one was used.