title: Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous (19)F and (31)P probes.
abstract: 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.
authors.affiliation: CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Ojugo
authors.forename: P M
authors.initials: PM
authors.lastname: McSheehy
authors.forename: D J
authors.initials: DJ
authors.lastname: McIntyre
authors.forename: C
authors.initials: C
authors.lastname: McCoy
authors.forename: M
authors.initials: M
authors.lastname: Stubbs
authors.forename: M O
authors.initials: MO
authors.lastname: Leach
authors.forename: I R
authors.initials: IR
authors.lastname: Judson
authors.forename: J R
authors.initials: JR
authors.lastname: Griffiths
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005461:Fluorine; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010758:Phosphorus; D014183:Transplantation, Heterologous
chemical_list: D010758:Phosphorus; D005461:Fluorine