Microscopic images of intraspheroidal pH by 1H magnetic resonance chemical shift imaging of pH sensitive indicators.

作者: Jose Alvarez-Pérez , Paloma Ballesteros , Sebastián Cerdán

DOI: 10.1007/S10334-005-0013-Z

关键词:

摘要: We investigate microscopic pH heterogeneity within tumor spheroids using a novel 1H NMR methodology that provides high resolution measurements of intraspheroidal pH. Material and Methods: High images were obtained by chemical shift selective excitation the H2 resonance imidazole added to incubation medium. Imidazole accumulated in space dependent manner. Maps could be transforming pixel (32 × 32$) regional variation intensity into relative scale. Results: Our analysis revealed drastic alterations depending on size spheroid, ca. 0.6 pH units more acidic necrotic core than periphery, for 600 μm diameter. The presence concentric regions having similar was consistently observed. thickness these decreased from pH 7.2 pH 6.8 increased below latter value. Conclusion: observations are compatible with general model spheroid growth where external layers cells active depict alkaline values while inner remain quiescent or evolve core, depicting values.

参考文章(40)
Brent P. Mahoney, Natarajan Raghunand, Brenda Baggett, Robert J. Gillies, Tumor acidity, ion trapping and chemotherapeutics: I. Acid pH affects the distribution of chemotherapeutic agents in vitro Biochemical Pharmacology. ,vol. 66, pp. 1207- 1218 ,(2003) , 10.1016/S0006-2952(03)00467-2
Zaver M. Bhujwalla, Dmitri Artemov, Eric Aboagye, Ellen Ackerstaff, Robert J. Gillies, Kshama Natarajan, Meiyappan Solaiyappan, The physiological environment in cancer vascularization, invasion and metastasis. Novartis Foundation symposium. ,vol. 240, pp. 23- 45 ,(2001) , 10.1002/0470868716.CH3
Anne Ziegler, Sebastián Cerdán, Régine Farion, Jonathan A. Coles, Chantal Rémy, Paloma Ballesteros, Gwénaël Hérigault, María-L. García-Martín, Mapping Extracellular pH in Rat Brain Gliomas in Vivo by H Magnetic Resonance Spectroscopic Imaging: Comparison with Maps of Metabolites Cancer Research. ,vol. 61, pp. 6524- 6531 ,(2001) , 10.13039/501100001677
J. R. Griffiths, D. J. O. McIntyre, F. A. Howe, M. Stubbs, Why are cancers acidic? A carrier-mediated diffusion model for H+ transport in the interstitial fluid. Novartis Foundation symposium. ,vol. 240, pp. 46- 67 ,(2008) , 10.1002/0470868716.CH4
P E Bock, C Frieden, Phosphofructokinase. II. Role of ligands in pH-dependent structural changes of the rabbit muscle enzyme. Journal of Biological Chemistry. ,vol. 251, pp. 5637- 5643 ,(1976) , 10.1016/S0021-9258(17)33105-8
Natarajan Raghunand, Robert J. Gillies, pH and chemotherapy. Novartis Foundation symposium. ,vol. 240, pp. 199- 211 ,(2001) , 10.1002/0470868716.CH14
R. P. Hill, K. De Jaeger, A. Jang, R. Cairns, pH, hypoxia and metastasis. Novartis Foundation symposium. ,vol. 240, pp. 154- 168 ,(2001) , 10.1002/0470868716.CH11
R. M. Sutherland, W. Mueller-Klieser, B. Sordat, J. Bamat, H. Gabbert, B. Bourrat, Oxygenation and differentiation in multicellular spheroids of human colon carcinoma. Cancer Research. ,vol. 46, pp. 5320- 5329 ,(1986)