Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous 19F and 31P probes

• Published in: NMR in biomedicine 1999-12, Vol.12 (8), p.495-504
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: 19F- and 31P-MRS; Biological and medical sciences; extracellular pH; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); pH gradient; solid tumours; Tumors
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/(SICI)1099-1492(199912)12:8<495::AID-NBM594>3.0.CO;2-K

Precise measurement of pHe in vivo may be of clinical value for both diagnosis and selection of therapy. pHe measurements made by the 31P probe 3‐aminopropylphosphonate (3‐APP) were compared with those made by the 19F 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 pHe were compared at 20–60 min post‐administration, although very low pHe values (ca. 6.0) were recorded in two out of eight Lettre tumours by ZK‐150471. The more rapid pHe measurements possible using ZK‐150471 showed that during the first 20 min post‐administration significant increases occurred in pHe 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 pHe 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 pHe by ZK‐150471 compared to 3‐APP. These characteristics suggest that ZK‐150471 is currently the preferred pHe probe for non‐invasive MRS. Copyright © 1999 John Wiley & Sons, Ltd.