Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jun;69(6):1083–1087. doi: 10.1038/bjc.1994.212

Magnetic resonance spectroscopic studies on 'real-time' changes in RIF-1 tumour metabolism and blood flow during and after photodynamic therapy.

J C Bremner 1, J K Bradley 1, I J Stratford 1, G E Adams 1
PMCID: PMC1969428  PMID: 8198974

Abstract

Magnetic resonance spectroscopy (MRS) in situ was used to study changes in 31P metabolism occurring during and after treatment of murine RIF-1 tumours with photodynamic therapy (PDT). Tumours were irradiated using a fibreoptic light delivery system while the mice were in position within the magnet. Changes in 31P-MRS were observable during and immediately after treatments of several minutes' duration. Both the extent and duration of the increase in the Pi/total ratio were light dose dependent. The effect on the metabolism was also affected by the time interval (TL) between administering the photosensitiser disulphonated phthalocyanine, (A1S2Pc) and the light. With a dose of 50 J the increase in Pi/total was much faster when TL was 1 h than when TL was 24 h. This difference in rate probably reflects differences in the distribution of A1S2Pc within the tumour. Significant decreases in pH were only seen after a light dose of 50 J when TL was 1 h. Blood flow measurements using deuterium uptake were also carried out using MRS. These experiments showed that for a dose of 50 J the level of blood flow was reduced by approximately 90% of the control value within 10 min from the end of the 8 min light treatment. This occurred irrespective of the value of TL. The data indicate that it is possible to observe very early changes in 31P metabolism that can be attributed to direct cellular damage as opposed to the later changes indicative of overall tumour hypoxia caused by vascular damage.

Full text

PDF
1083

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams G. E., Bremner J. C., Stratford I. J., Wood P. J. Can 31P magnetic resonance spectroscopy measurements of changes in experimental tumour metabolism be related to modification of oxygenation status? BJR Suppl. 1992;24:137–141. [PubMed] [Google Scholar]
  2. Ambroz M., Beeby A., MacRobert A. J., Simpson M. S., Svensen R. K., Phillips D. Preparative, analytical and fluorescence spectroscopic studies of sulphonated aluminium phthalocyanine photosensitizers. J Photochem Photobiol B. 1991 Apr;9(1):87–95. doi: 10.1016/1011-1344(91)80006-4. [DOI] [PubMed] [Google Scholar]
  3. Berns M. W., Dahlman A., Johnson F. M., Burns R., Sperling D., Guiltinan M., Siemens A., Walter R., Wright W., Hammer-Wilson M. In vitro cellular effects of hematoporphyrin derivative. Cancer Res. 1982 Jun;42(6):2325–2329. [PubMed] [Google Scholar]
  4. Bremner J. C., Adams G. E., Pearson J. K., Sansom J. M., Stratford I. J., Bedwell J., Bown S. G., MacRobert A. J., Phillips D. Increasing the effect of photodynamic therapy on the RIF-1 murine sarcoma, using the bioreductive drugs RSU1069 and RB6145. Br J Cancer. 1992 Dec;66(6):1070–1076. doi: 10.1038/bjc.1992.412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ceckler T. L., Bryant R. G., Penney D. P., Gibson S. L., Hilf R. 31P-NMR spectroscopy demonstrates decreased ATP levels in vivo as an early response to photodynamic therapy. Biochem Biophys Res Commun. 1986 Oct 15;140(1):273–279. doi: 10.1016/0006-291x(86)91086-7. [DOI] [PubMed] [Google Scholar]
  6. Chapman J. D., McPhee M. S., Walz N., Chetner M. P., Stobbe C. C., Soderlind K., Arnfield M., Meeker B. E., Trimble L., Allen P. S. Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors. J Natl Cancer Inst. 1991 Nov 20;83(22):1650–1659. doi: 10.1093/jnci/83.22.1650. [DOI] [PubMed] [Google Scholar]
  7. Chopp M., Farmer H., Hetzel F., Schaap A. P. In vivo 31P-NMR spectroscopy of mammary carcinoma subjected to subcurative photodynamic therapy. Photochem Photobiol. 1987 Nov;46(5):819–822. doi: 10.1111/j.1751-1097.1987.tb04853.x. [DOI] [PubMed] [Google Scholar]
  8. Chopp M., Hetzel F. W., Jiang Q. Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy. Radiat Res. 1990 Mar;121(3):288–294. [PubMed] [Google Scholar]
  9. Henderson B. W., Waldow S. M., Mang T. S., Potter W. R., Malone P. B., Dougherty T. J. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res. 1985 Feb;45(2):572–576. [PubMed] [Google Scholar]
  10. Hilf R., Gibson S. L., Penney D. P., Ceckler T. L., Bryant R. G. Early biochemical responses to photodynamic therapy monitored by NMR spectroscopy. Photochem Photobiol. 1987 Nov;46(5):809–817. doi: 10.1111/j.1751-1097.1987.tb04852.x. [DOI] [PubMed] [Google Scholar]
  11. Mattiello J., Evelhoch J. L., Brown E., Schaap A. P., Hetzel F. W. Effect of photodynamic therapy on RIF-1 tumor metabolism and blood flow examined by 31P and 2H NMR spectroscopy. NMR Biomed. 1990 Apr;3(2):64–70. doi: 10.1002/nbm.1940030204. [DOI] [PubMed] [Google Scholar]
  12. Selman S. H., Kreimer-Birnbaum M., Klaunig J. E., Goldblatt P. J., Keck R. W., Britton S. L. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light. Cancer Res. 1984 May;44(5):1924–1927. [PubMed] [Google Scholar]
  13. Singh G., Jeeves W. P., Wilson B. C., Jang D. Mitochondrial photosensitization by Photofrin II. Photochem Photobiol. 1987 Nov;46(5):645–649. doi: 10.1111/j.1751-1097.1987.tb04826.x. [DOI] [PubMed] [Google Scholar]
  14. Stratford I. J., Adams G. E., Godden J., Nolan J., Howells N., Timpson N. Potentiation of the anti-tumour effect of melphalan by the vasoactive agent, hydralazine. Br J Cancer. 1988 Aug;58(2):122–127. doi: 10.1038/bjc.1988.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Twentyman P. R., Brown J. M., Gray J. W., Franko A. J., Scoles M. A., Kallman R. F. A new mouse tumor model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst. 1980 Mar;64(3):595–604. [PubMed] [Google Scholar]
  16. van Bruggen N., Chan W. S., Syha J., Marshall J. F., Proctor E., Williams S. R., Gadian D. G., Hart I. R. Cell and tissue responses of a murine tumour to phthalocyanine-mediated photodynamic therapy. Eur J Cancer. 1992;28(1):42–46. doi: 10.1016/0959-8049(92)90381-b. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES