Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Jun;63(6):916–922. doi: 10.1038/bjc.1991.201

Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy.

T L Ceckler 1, S L Gibson 1, S D Kennedy 1, R Hill 1, R G Bryant 1
PMCID: PMC1972526  PMID: 1829953

Abstract

Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (Pi) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in Pi were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in Pi resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned a near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis.

Full text

PDF
916

Images in this article

Selected References

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

  1. Ackerman J. J., Lowry M., Radda G. K., Ross B. D., Wong G. G. The role of intrarenal pH in regulation of ammoniagenesis: [31P]NMR studies of the isolated perfused rat kidney. J Physiol. 1981;319:65–79. doi: 10.1113/jphysiol.1981.sp013892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Brown T. R., Kincaid B. M., Ugurbil K. NMR chemical shift imaging in three dimensions. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3523–3526. doi: 10.1073/pnas.79.11.3523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. 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]
  7. Dodd N. J., Moore J. V., Poppitt D. G., Wood B. In vivo magnetic resonance imaging of the effects of photodynamic therapy. Br J Cancer. 1989 Aug;60(2):164–167. doi: 10.1038/bjc.1989.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fingar V. H., Henderson B. W. Drug and light dose dependence of photodynamic therapy: a study of tumor and normal tissue response. Photochem Photobiol. 1987 Nov;46(5):837–841. doi: 10.1111/j.1751-1097.1987.tb04856.x. [DOI] [PubMed] [Google Scholar]
  9. Gibson S. L., Ceckler T. L., Bryant T. G., Hilf R. Effects of laser photodynamic therapy on tumor phosphate levels and pH assessed by 31P-NMR spectroscopy. Cancer Biochem Biophys. 1989 Oct;10(4):319–328. [PubMed] [Google Scholar]
  10. Gibson S. L., Hilf R. Photosensitization of mitochondrial cytochrome c oxidase by hematoporphyrin derivative and related porphyrins in vitro and in vivo. Cancer Res. 1983 Sep;43(9):4191–4197. [PubMed] [Google Scholar]
  11. HILF R., MICHEL I., BELL C., FREEMAN J. J., BORMAN A. BIOCHEMICAL AND MORPHOLOGIC PROPERTIES OF A NEW LACTATING MAMMARY TUMOR LINE IN THE RAT. Cancer Res. 1965 Apr;25:286–299. [PubMed] [Google Scholar]
  12. 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]
  13. Hilf R., Murant R. S., Narayanan U., Gibson S. L. Relationship of mitochondrial function and cellular adenosine triphosphate levels to hematoporphyrin derivative-induced photosensitization in R3230AC mammary tumors. Cancer Res. 1986 Jan;46(1):211–217. [PubMed] [Google Scholar]
  14. Hilf R., Smail D. B., Murant R. S., Leakey P. B., Gibson S. L. Hematoporphyrin derivative-induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230AC mammary adenocarcinomas of rats. Cancer Res. 1984 Apr;44(4):1483–1488. [PubMed] [Google Scholar]
  15. Kessel D. In vivo fluorescence of tumors after treatment with derivatives of hematoporphyrin. Photochem Photobiol. 1986 Jul;44(1):107–108. doi: 10.1111/j.1751-1097.1986.tb03571.x. [DOI] [PubMed] [Google Scholar]
  16. Naruse S., Higuchi T., Horikawa Y., Tanaka C., Nakamura K., Hirakawa K. Radiofrequency hyperthermia with successive monitoring of its effects on tumors using NMR spectroscopy. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8343–8347. doi: 10.1073/pnas.83.21.8343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Naruse S., Horikawa Y., Tanaka C., Higuchi T., Sekimoto H., Ueda S., Hirakawa K. Evaluation of the effects of photoradiation therapy on brain tumors with in vivo P-31 MR spectroscopy. Radiology. 1986 Sep;160(3):827–830. doi: 10.1148/radiology.160.3.3737923. [DOI] [PubMed] [Google Scholar]
  18. Nelson J. S., Liaw L. H., Orenstein A., Roberts W. G., Berns M. W. Mechanism of tumor destruction following photodynamic therapy with hematoporphyrin derivative, chlorin, and phthalocyanine. J Natl Cancer Inst. 1988 Dec 21;80(20):1599–1605. doi: 10.1093/jnci/80.20.1599. [DOI] [PubMed] [Google Scholar]
  19. Ng T. C., Glickson J. D. Shielded solenoidal probe for in vivo NMR studies of solid tumors. Magn Reson Med. 1985 Apr;2(2):169–175. doi: 10.1002/mrm.1910020207. [DOI] [PubMed] [Google Scholar]
  20. Rodrigues L. M., Midwood C. J., Coombes R. C., Stevens A. N., Stubbs M., Griffiths J. R. 31P-nuclear magnetic resonance spectroscopy studies of the response of rat mammary tumors to endocrine therapy. Cancer Res. 1988 Jan 1;48(1):89–93. [PubMed] [Google Scholar]
  21. Sandberg S., Romslo I. Porphyrin-sensitized photodynamic damage of isolated rat liver mitochondria. Biochim Biophys Acta. 1980 Dec 3;593(2):187–195. doi: 10.1016/0005-2728(80)90056-0. [DOI] [PubMed] [Google Scholar]
  22. Schneckenburger H., Feyh J., Götz A., Frenz M., Brendel W. Quantitative in vivo measurement of the fluorescent components of Photofrin II. Photochem Photobiol. 1987 Nov;46(5):765–768. doi: 10.1111/j.1751-1097.1987.tb04845.x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Star W. M., Marijnissen H. P., van den Berg-Blok A. E., Versteeg J. A., Franken K. A., Reinhold H. S. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res. 1986 May;46(5):2532–2540. [PubMed] [Google Scholar]
  25. Stenstrøm A. G., Moan J., Brunborg G., Eklund T. Photodynamic inactivation of yeast cells sensitized by hematoporphyrin. Photochem Photobiol. 1980 Sep;32(3):349–352. doi: 10.1111/j.1751-1097.1980.tb03773.x. [DOI] [PubMed] [Google Scholar]
  26. Sweetenham J. W., McKendrick J. J., Jones D. H., Whitehouse J. M., Williams C. J. High dose intensity combination chemotherapy for advanced epithelial ovarian carcinoma: results of a pilot study. Br J Cancer. 1990 Feb;61(2):319–322. doi: 10.1038/bjc.1990.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. West-Jordan J. A., Smith A., Myint S., Gardner J. A., Abraham R. J., Edwards R. H., Warenius H. M. 31P NMR studies on recovery from hypoxia of human tumor cells. Magn Reson Med. 1987 Aug;5(2):182–185. doi: 10.1002/mrm.1910050211. [DOI] [PubMed] [Google Scholar]
  28. Wilson B. C., Jeeves W. P., Lowe D. M. In vivo and post mortem measurements of the attenuation spectra of light in mammalian tissues. Photochem Photobiol. 1985 Aug;42(2):153–162. doi: 10.1111/j.1751-1097.1985.tb01554.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES