Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo.

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.

The cell transmembrane pH gradient in tumors enhances cytotoxicity of specific weak acid chemotherapeutics.

The extracellular pH is lower in tumor than in normal tissue, whereas their intracellular pH is similar. In this study, we show that the tumor-specific pH gradient may be exploited for the treatment of cancer by weak acid chemotherapeutics. i.v.-injected glucose substantially decreased the electrode estimated extracellular pH in a xenografted human tumor while its intracellular pH, evaluated by (31)P magnetic resonance spectroscopy, remained virtually unchanged. The resulting increase in the average cell pH gradient caused a parallel increase in tumor growth delay by the weak acid chlorambucil (CHL). Regardless of glucose administration, the effect of CHL was significantly greater in tumors preirradiated with a large dose of ionizing radiation. This suggests that CHL was especially pronounced in radioresistant hypoxic cells possessing a larger transmembrane pH gradient. These results indicate that the naturally occurring cell pH gradient difference between tumor and normal tissue is a major and exploitable determinant of the uptake of weak acids in the complex tumor microenvironment. The use of such drugs may be especially effective in combination with radiation.

[Changes in the replication apparatus and phosphorus-containing metabolite pool in experimental tumors in animals during development]. / Izmeneniia v apparate replikatsii i sostoianii pula fosforsoderzhashchikh metabolitov éksperimental'nykh opukholei zhivotnykh v protsesse razvitiia.

Activity of replicase complex enzymes involving thymidine kinase (TK), ribonucleotide reductase (RR), DNA-polymerases alpha and beta as well as DNA synthesis and single breaks in DNA were studied during growth of P388 ascites tumor. Under these conditions the rate of DNA synthesis was distinctly decreased via salvage pathway and de novo. Single breaks were not detected in the preexistent DNA within various periods after transplantation of P338 leukemic cells. Retardation of DNA synthesis during tumor growth correlated with a decrease in TK, RR and DNA-polymerase alpha activities, while DNA-polymerase beta activity was markedly increased. Growth of melanoma B16 was accompanied by a decrease in content of ATP, ADP, NAD, phosphocreatine and phosphosaccharides as well as by an increase in the level of inorganic phosphates.

[Recording of high resolution 31P NMR spectra from the surface of a living object]. / Registratsiia spektrov IaMR P vysokogo razresheniia s poverkhnosti zhivogo ob"ekta.

A surface coil probehead was worked out for the superconducting 50 mm bore magnet of NMR a high resolution NMR spectrometer with the field strength 8,46 T (145.78 MHz for 31P nuclei) with a 50 mm slot. The requirements were analysed for the surface R.F. coil to obtain the greatest possible single/noise ratio at fixed space selectivity. Real penetration depth of the radio-frequency field into the specimen was estimated. Spectra of liver and abdominal muscle of anesthetized mouse were obtained. The probehead may be applied to obtain high resolution 31P spectra in vivo studies of animal organs.