Dual-time-point (18)F-FDG-PET/CT imaging in the assessment of suspected malignancy.

UNLABELLED: INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. METHODS: A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. RESULTS: Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. CONCLUSIONS: (18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.

Catalytic asymmetric Claisen rearrangement of unactivated allyl vinyl ethers.

Nearly a century after their original discovery, catalyzed enantioselective variants of the venerable Claisen rearrangement remain relatively rare. We have discovered a cooperative transition metal-Lewis acid cocatalyst system that affects highly enantio- and diastereoselective examples of archetypical Claisen rearrangements. The catalyzed rearrangements proceed using an easily prepared enantioenriched transition metal catalyst and a commercially available Lewis acid cocatalyst at ambient temperature in common solvents.

Contrasting responses of pyrido[2,1-a]isoindol-6-ones and their sultam counterparts to photochemical activation.

A ring-closing metathesis-based strategy has allowed access to an unreported pair of pyridoisoindolones and their previously unknown sultam counterparts. The synthetic routing takes advantage of the ready availability of N-allylphthalimide and N-allylsaccharin and proceeds via the proper incorporation of small side chains into the heterocyclic ring. Positionally selective introduction of the conjugated diene functionality was realized efficiently. Detailed study of the excited-state chemistry of 7 and 8 showed both lactams to be subject to [4 + 2] dimerization under acetone-sensitized conditions. Different regioselectivities are involved, with the response of 8 being far more efficient than that exhibited by 7. No dimers could be isolated from the photolyzates of 9 and 10 under any conditions. While the latter sultam undergoes extensive polymerization, 9 is transformed via direct irradiation at 350 nm into 46 and 47 via [1,3]-sigmatropy involving the S-N bond and heterocyclic ring cleavage, respectively.

7-Bromo-4b-methyl-7,8-dihydro-4bH-9-thia-8a-aza-fluorene 9,9-dioxide.

The title compound, C(12)H(12)BrNO(2)S, was isolated after direct irradiation (hν 350 nm, hexa-ne) of a mixture of stereoisomeric sulfonamides containing a vicinal dibromide and a conjugated diene. This product is one of a group of substrates that has contributed to our understanding of the photoreactivity patterns of non-bridged sulfonamides. The crystal structure was determined from a non-merohedrally twinned data set, where the twin law corresponded to a 180° rotation about the a* axis. The minor twin component refined to a value of 0.176 (3). The conformation of the mol-ecule is planar at one end, as the benzene ring and the adjacent fused five-membered ring are coplanar, and U-shaped at the other end, where the five-membered ring is fused to the heterocyclic six-membered ring containing an allyl bromide group.

(+)-(1S,5R,10S)-11,11-Dimeth-yl-4-oxa-tricyclo-[8.4.0.0]tetra-deca-ne-3,12-dione.

The title compound, C(15)H(22)O(3), was prepared via amino-acid-promoted Robinson annulation followed by tandem Pd/C-mediated hydrogenation and oxidative cyclization. This product was instrumental in determining the feasibility of a stereocontrolled hydrogenation in which the directing hydroxyl group is adjacent to the 6-7-ring network and its olefinic component. The asymmetric unit consists of a single mol-ecule with normal geometric parameters. The absolute configuration was assigned based on the known enanti-omeric prescursor. Inter-molecular C-H⋯O inter-actions link each mol-ecule with four neighboring mol-ecules.

Direct comparison of the response of bicyclic sultam and lactam dienes to photoexcitation. Concerning the propensity of differing bond types to bridgehead nitrogen for homolytic cleavage.

A convergent strategy has allowed access to bridgehead sultam 9 and the related carboxamides 10 and 11. The synthetic routing proceeds via the coupling of a suitably constructed dienamine to either o-iodobenzenesulfonyl chloride or o-iodobenzoyl chloride to generate the amides. The application in sequence of ring-closing metathesis and an intramolecular Heck reaction gave rise to advanced tricyclic intermediates. The final two steps involved bromination in liquid bromine and proper 2-fold dehydrobromination. The latter maneuver was best achieved with tetrabutylammonium fluoride in DMSO at elevated temperature. While the irradiation of 9 led principally via SO2-N bond homolysis and [1,5] sigmatropic rearrangement to generate 37, 10 proceeded via disrotatory cyclization to the exo cyclobutene 39, and 11 resisted photoisomerization. The inertness of 11 may stem from its distorted structural features which force its conjugated diene double bonds to be rigidly oriented 32 degrees out-of-plane. The unique ability of the sulfonamide linkage to excited-state homolysis holds comparative interest.

Ring contraction of bridgehead sultams by photoinduced di-pi-methane rearrangement.

Triplet-sensitized irradiation of 8-thia-9-azatricyclo[7.2.1.0(2,7)]dodeca-2,4,6,10-tetraene (16) in acetone solution gives rise exclusively to tetracyclic sultam 20. This strong preference for benzo-vinyl bridging distal to the sulfonamide functional group has also been observed in eight derivatives carrying chemically diverse functional groups at C-10. In none of these examples is regiospecificity eroded. This overall result suggests that the added substituents act in harmony with the electronic rebonding pathway found operative in the parent system. From the structural perspective, this transformation constitutes a facile means for accomplishing the ring contraction of a bridgehead sultam.