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

NMR Biomed. 1999 Dec;12(8):495-504. doi: 10.1002/(sici)1099-1492(199912)12:8<495::aid-nbm594>;2-k.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Fluorine
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Inbred C3H
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / metabolism*
  • Phosphorus
  • Transplantation, Heterologous


  • Phosphorus
  • Fluorine