Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.     

IV. Referate

Ohne Zusammenfassung     

Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains

Nitrogen-starved diploid cells of the yeast Saccharomyces cerevisiae differentiate into a filamentous, pseudohyphal growth form. Recognition of nitrogen starvation is mediated, at least in part, by the ammonium permease Mep2p and the Galpha subunit Gpa2p. Genetic activation of the pheromone-responsive MAP kinase cascade, which is also required for filamentous growth, only weakly suppresses the filamentation defect of Deltamep2/Deltamep2 and Deltagpa2/Deltagpa2 strain. Surprisingly, deletion of Mep1p, an ammonium permease not previously thought to regulate differentiation, significantly enhances the potency of MAP kinase activation, such that the STE11-4 allele induces filamentation to near wild-type levels in Deltamep1/Deltamep1 Deltamep2/Deltamep2 and Deltamep1/Deltamep1 Deltagpa2/Deltagpa2 strains. To identify additional regulatory components, we isolated high-copy suppressors of the filamentation defect of the Deltamep1/Deltamep1 Deltamep2/Deltamep2 mutant. Multicopy expression of TEC1, PHD1, PHD2 (MSS10/MSN1/FUP4), MSN5, CDC6, MSS11, MGA1, SKN7, DOT6, HMS1, HMS2, or MEP2 each restored filamentation in a Deltamep1/Deltamep1 Deltamep2/Deltamep2 strain. Overexpression of SRK1 (SSD1), URE2, DAL80, MEP1, or MEP3 suppressed only the growth defect of the Deltamep1/Deltamep1 Deltamep2/Deltamep2 mutant strain. Characterization of these genes through deletion analysis and epistasis underscores the complexity of this developmental pathway and suggests that stress conditions other than nitrogen deprivation may also promote filamentous growth.     

Thermomechanical calculations related to thermally induced rock loosening in an underground cavity

Zones of loosening, together with failure probability and safety factors, can be used to characterize the stability of underground caverns. The effect of a cylindrical heat source on the surrounding rock salt has been investigated in an in situ test carried out in a rock salt mass at a depth of about 750 m. The results of the calculations were confirmed by comparison with the temperatures and displacements measured during the in situ experiment.     

The determination of corrosion rates by electrochemical d.c. and a.c. methods — II. Systems with discontinuous steady state polarization behavior

Corrosion systems exhibiting discontinuous anodic polarization curves have been investigated by steady state polarization, linear sweep polarization, large and small signal pulse polarization, a.c. impedance measurements and solution analysis. It is shown that the true corrosion current density can only be determined if the non-linearity of the system is avoided. This is not possible from analysis of a.c. impedance results without model assumptions.     

Information transport and computation in nanometre-scale structures

We discuss two examples of novel information-transport and processing mechanisms in nanometre-scale structures. The local modulation and detection of a quantum state can be used for information transport at the nanometre length-scale, an effect we call a 'quantum mirage'. We demonstrate that, unlike conventional electronic information transport using wires, the quantum mirage can be used to pass multiple channels of information through the same volume of a solid. We discuss a new class of nanometre-scale structures called 'molecule cascades', and show how they may be used to implement a general-purpose binary-logic computer in which all of the circuitry is at the nanometre length-scale.