Syntheses of 5-(2-[F-18]fluoroethyl)- 5-(2[Br-80]bromoethyl)- (2), undeprotected (E)-5-(2-[F-18]fluorovinyl)- (3) and (E)-5-(2-[Br-80]bromovinyl)-2'-deoxyuridines (4). as the tracers for monitoring cancer gene therapy with positron emission tomography were described. Decay corrected radiochemical yield and synthesis time including labeling and HPLC purification from end of bombardment for 1 was 9.5% and 2 hours,. respectively; yield and time for 2 was 16% and 2 hours, respectively. Chemical (approximate to radiochemical) yield and time for synthesis of 3 was 7.5% and 7 minutes, respectively. Radiochemical yield and synthesis, time including labeling and HPLC purification of an analytical sample of 4 was 60% and 30 minutes, respectively. Both 2 and 4 received the side reactions during HPLC purification, i.e. ring closure and cleavage of glycosidic bond, respectively. Application of 2 and 4 needed to be confirmed by in vitro or in vivo experiments. Radiochemical yield of 1 could be optimized by employing a modified protocol for preparation of its precursor. The preparation of fluorovinyl counterparts had demonstrated the potential utility of the stannane, 3-tolyl-3',5'-di-O-acetyl-(E)-5-(2-stannyl-vinyl)-2'-deoxyuridine 7. Copyright (C) 2003 John Wiley Sons, Ltd.

[11C]Thymidine has been used as a proliferation marker in positron-emission-tomography (PET) studies of tumors. This compound showed metabolite related problems and the radiosynthesis proved to be difficult. Recently, the more stable 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been suggested as an alternative. One advantage of [18F]FLT is based on thymidine kinase-1 catalyzed phosphorylation of FLT and the intracellular accumulation of this metabolite without participation in DNA synthesis. The radiosynthesis of [18F]FLT originally designed by Grierson et al. was found to be demanding especially regarding the workup of the [18F]fluoride/1-(2-deoxy-3-O-nosyl-5-O-DMT-β-D-threo-pento-furanosyl)-3-DMBn-thymine reaction mixture. Instead, we used 2,3′-anhydro-5′-O-(4,4′-dimethoxytrityl)thymidine as a precursor for the synthesis of [18F]FLT. In DMSO at 175°C and in presence of Kryptofix® 2.2.2. we obtained 5.6± 1,4% [18F]FLT (EOS). Copyright © 2000 John Wiley & Sons, Ltd.

With the aim of investigation, the mechanisms of resistance to methotrexate (MTX) in children refractory to leukaemia-treatment, we established a method of analysing MTX metabolism in Nalm6 cells (human pre-B). The optimal extracellular concentration for MTX uptake and MTX polyglutamate (MTXPG2-6) formation at a density of 5 x 10(6) cells/ml was 1 microM 3H-MTX. After 15 h incubation at this concentration, a plateau of 5 pmol/10(6) cells of total MTX accumulated in the form of equal amounts of polyglutamates 3, 4 and 5 and low amounts of MTX and polyglutamates 2 and 6. MTX preloaded cells rapidly lost MTX and MTXPG2 in MTX-free medium, while MTXPG5 was still formed and then degraded very slowly. After 8 h in medium without MTX, 40% of total MTXPG was lost, after 24 h, 70%. The method is feasible for patient blasts. The number of blasts isolated from bone marrow after diagnosis is enough to perform small kinetic studies. The uptake of MTX into patient blasts is about 1/10 of that in Nalm6 cells.

Several nucleoside analogues like 1-(beta-D-glucopyranosyl)-5-fluorouracil 10, 1-(beta-D-galactopyranosyl)-5-fluorouracil 11 and 1-(2-deoxy-beta-D-glucopyranosyl)-5-fluorouracil 12 have been synthesized. From the corresponding 1-(2',3',4',6'-tetra-O-acetyl-beta-D-glycopyranosyl)-uracils 4, 5 and 6, the F-18 labelled compounds 16, 17 and 18 have been prepared via the intermediates 13, 14 and 15 in acetic acid using [F-18]F-2 and acidic deacetylating procedures. The F-18 labelled derivatives could be obtained, following preparative chromatography, in high purity and in yields of about 3 . 10(8) Bq - 5.7 . 10(8) Bq (18% - 34% related to the trapped radioactivity, not corrected for decay) for their in-vine evaluation and for in-vivo studies with PET.

It is generally assumed that thiol anticarcinogens like disulfiram (DSF) or sodium 2-mercaptoethane-sulfonate (mesna) after in vivo administration react rapidly with serum protein sulfhydryl groups forming mixed disulfides. Different methods have been established for the synthesis of mixed disulfides between cysteine or glutathione and diethyldithiocarbamate (DDTC) or mesna in order to elucidate their chemical and biological effects. A short summary is given of pilot biochemical experiments carried out with two mixed disulfides.