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Titolo:
Mapping extracellular pH in rat brain gliomas in vivo by H-1 magnetic resonance spectroscopic imaging: Comparison with maps of metabolites
Autore:
Garcia-Martin, ML; Herigault, G; Remy, C; Farion, R; Ballesteros, P; Coles, JA; Cerdan, S; Ziegler, A;
Indirizzi:
CSIC, Inst Invest Biomed, E-28029 Madrid, Spain CSIC Madrid Spain E-28029 SIC, Inst Invest Biomed, E-28029 Madrid, Spain Univ Grenoble 1, INSERM, U438, CHU,CEA, F-38043 Grenoble, France Univ Grenoble 1 Grenoble France F-38043 HU,CEA, F-38043 Grenoble, France Univ Nacl Educ Distancia, Fac Ciencias, Dept Quim Organ & Biol, E-28040 Madrid, Spain Univ Nacl Educ Distancia Madrid Spain E-28040 iol, E-28040 Madrid, Spain
Titolo Testata:
CANCER RESEARCH
fascicolo: 17, volume: 61, anno: 2001,
pagine: 6524 - 6531
SICI:
0008-5472(20010901)61:17<6524:MEPIRB>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VIVO; TUMOR PH; SOLVENT SUPPRESSION; SOLID TUMORS; LACTIC-ACID; BLOOD-FLOW; C6 GLIOMA; LACTATE; NMR; H-1-NMR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Ziegler, A INSERM, U438, CHU Pavillon B,BP 217, F-38043 Grenoble 9, FranceINSERM CHU Pavillon B,BP 217 Grenoble France 9 noble 9, France
Citazione:
M.L. Garcia-Martin et al., "Mapping extracellular pH in rat brain gliomas in vivo by H-1 magnetic resonance spectroscopic imaging: Comparison with maps of metabolites", CANCER RES, 61(17), 2001, pp. 6524-6531

Abstract

The value of extracellular pH (pH(e)) in tumors is an important factor in prognosis and choice of therapy. We demonstrate here that pH(e) can be mapped in vivo in a rat brain glioma by H-1 magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionicacid (IEPA). H-1 S1 also allowed us to map metabolites, and, to better understand the determinants of pH(e), we compared maps of pH(e), metabolites, and the distribution of the contrast agent gadolinium1,4,7,10-tetraazacyclododecane-N,N',N : ,N'"-tetraaceticacid (Gd-DOTA). C6 cells injected in caudate nuclei of four Wistar rats gave rise to gliomas of similar to 10 nim indiameter. Three mmols of IEPA were injected in the right jugular vein fromt = 0 to t = 60 min. From t = 50 min to t = 90 min, spin-echo H-1 S1 was performed with an echo time of 40 ms in a 2.5-mm slice including the glioma (nominal voxel size, 2.2 mul). IEPA resonances were detected only within the glioma and were intense enough for pH(e) to be calculated from the chemical shift of the H2 resonance in almost all voxels of the glioma. H-1 spectroscopic images with an echo time of 136 ms were then acquired to map metabolites: lactate, choline-containing compounds (tCho), phosphocreatine/creatine, and N-acetylaspartate. Finally, T-1-weighted imaging after injection ofa bolus of Gd-DOTA gave a map indicative of extravasation. On average, thegradient of pH(e) (measured where sufficient IEPA was present) from the center to the periphery was not statistically significant. Mean pH(e) was calculated for each of the four gliomas, and the average was 7.094 +/- 0.017 (/- SE; n = 4 rats), which is acid with respect to pH(e) of normal tissue. After normalization of spectra to their water peak, voxel-by-voxel comparisons of peak areas showed that N-acetylaspartate, a marker of neurons, correlated negatively with IEPA (P < 0.0001) and lactate (P < 0.05), as expectedof a glioma surrounded by normal tissue. tCho (which may indicate proliferation) correlated positively with pH(e) (P < 0.0001). Lactate correlated positively with tCho (P < 0.0001), phosphocreatine/creatine (P < 0.001), and Gd-DOTA (P < 0.0001). Although lactate is exported from cells in association with protons, within the gliomas, no evidence was observed that pH(e) wassignificantly lower where lactate concentration was higher. These results suggest that lactate is produced mainly in viable, well-perfused, tumoral tissue from which proton equivalents are rapidly cleared.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 08:06:23