Recognition of cancer in vivo by nuclear magnetic resonance.

Pulsed nuclear magnetic resonance has been used to differentiate in vivo between normal mouse tail tissue and a malignant transplanted melanoma, S91, located on the tail. The tumor displayed a nuclear (proton) spin-lattice relaxation time of approximately 0.7 second contrasted with the simultaneously measured normal tail tissue relaxation time of approximately 0.3 second.

Nitric oxide-mediated regulation of chemosensitivity in cancer cells.

BACKGROUND: Hypoxia in tumors is associated with malignant progression, metastatic spread, and increased resistance to radiotherapy and chemotherapy. Molecular O(2) is required for the cellular production of nitric oxide (NO) by the enzyme NO synthase (NOS), and NO may block components of the adaptive response to hypoxia. Hence, we hypothesized that hypoxia increases drug resistance in tumor cells by inhibiting endogenous NO production. METHODS: Human breast carcinoma (MDA-MB-231) and mouse melanoma (B16F10) cells were pre-exposed to 20% O(2), 5% O(2), or 1% O(2), incubated with a pharmacologic inhibitor of endogenous NO production, and then treated with chemotherapeutic agents. Resistance was assessed by colony-formation assays, and western blot analysis was used to measure NOS protein levels. All P values were two-sided. RESULTS: Incubation of MDA-MB-231 tumor cells in 1% O(2) maximally increased their resistance to doxorubicin and 5-fluorouracil by 8.5-fold (P =.002) and 2.3-fold (P =.002), respectively, compared with incubation in 20% O(2). B16F10 mouse melanoma cells preincubated in 1% O(2) (versus 20% O(2)) for 12 hours exhibited a twofold increase in resistance to doxorubicin (P<.001). The rapid acquisition of drug resistance after exposure to 1% O(2) could be mimicked by incubating the MDA-MB-231 cells for 12 hours with the NOS inhibitor N(G)-monomethyl-Larginine (fivefold increase; P<.001). Conversely, replacement of NO activity by use of the NO-mimetic glyceryl trinitrate (GTN) and diethylenetriamine NO adduct produced statistically significant attenuations in the development of resistance of 59% (P<.001) and 40% (P<.001), respectively, in MDA-MB-231 cells. Treatment of B16F10 cells with GTN produced a 58% reduction in resistance (P<.001). MDA-MB-231 cells expressed all three isoforms of the NOS enzyme at levels that were not altered by exposure to hypoxia. CONCLUSIONS: NO mediates chemosensitivity in tumor cells, and hypoxia-induced drug resistance appears to result, in part, from downstream suppression of endogenous NO production. These results raise the possibility that administration of small doses of NO mimetics could be used as an adjuvant in chemotherapy.

Behavior of different nuclear probes for detection of cancer by nuclear magnetic resonance.

A physical explanation is given for the finding that the spin-lattice relaxation time T1, obtained by nuclear magnetic resonance from equivalent malignant and non-malignant samples, is greater for the phosphorus isotype 31P than for the proton 1H. The nuclear relaxation of the phosphorus proceeds by way of its interaction with associated cell water. Within limits determined by other variables, T1 is expected to vary inversely as the square of the gyromagnetic ratio.

Cancer Detection by NMR in the Living Animal.

The purpose of this paper is to review in vivo NMR experiments [1, 2] on a transplantable tumor in mice and to discuss the feasibility of using noninvasive NMR for cancer detection in humans.