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Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous 19 F and 31 P probes
Author(s) -
Ojugo Agatha S. E.,
McSheehy Paul M. J.,
McIntyre Dominick J. O.,
McCoy Cheryl,
Stubbs Marion,
Leach Martin O.,
Judson Ian R.,
Griffiths John R.
Publication year - 1999
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/(sici)1099-1492(199912)12:8<495::aid-nbm594>3.0.co;2-k
Subject(s) - extracellular , chemistry , in vivo , nuclear magnetic resonance , penetration (warfare) , analytical chemistry (journal) , nuclear medicine , nuclear chemistry , chromatography , medicine , biochemistry , biology , physics , microbiology and biotechnology , operations research , engineering
Precise measurement of pH e in vivo may be of clinical value for both diagnosis and selection of therapy. pH e measurements made by the 31 P probe 3‐aminopropylphosphonate (3‐APP) were compared with those made by the 19 F probe, 3‐[ N ‐(4‐fluor‐2‐trifluoromethylphenyl)‐sulphamoyl]‐propionic acid (ZK‐150471) in three solid tumour types, human HT29 xenografts, murine RIF‐1 fibrosarcomas and Lettre tumours grown subcutaneously in mice. No significant differences were observed when probe measurements of pH e were compared at 20–60 min post‐administration, although very low pH e values (ca. 6.0) were recorded in two out of eight Lettre tumours by ZK‐150471. The more rapid pH e measurements possible using ZK‐150471 showed that during the first 20 min post‐administration significant increases occurred in pH e which were greatest in the more necrotic tumours. Since isolated cell experiments showed that ZK‐150471 was non‐toxic and did not enter the cells, this early increase in pH e may reflect gradual penetration by ZK‐150471 of the reportedly alkaline necrotic space in the tumours. The wide chemical shift range, improved signal‐to‐noise and absence of signal overlap allowed a more rapid and precise measurement of pH e by ZK‐150471 compared to 3‐APP. These characteristics suggest that ZK‐150471 is currently the preferred pH e probe for non‐invasive MRS. Copyright © 1999 John Wiley & Sons, Ltd.