Abstract
Magnetic resonance spectroscopy in situ was used to study changes in phosphorus 31 metabolism after photodynamic therapy (PDT) of transplanted HeLa cell tumours. Tumours were irradiated 2 h after administration of ATX-S10 (8-formyloximethylidene-7-hydroxy-3-ethenyl-2,7,12,18, tetramethyl-porphyrin-13,17-bispropionil aspartate), a new photosensitizer and chlorin derivative. Nuclear magnetic resonance spectra were measured prior to illumination and 1, 3, 7, 14, 21 and 28 days after PDT on each mouse. A drastic decrease in adenosine triphosphate (ATP) and a concomitant increase in inorganic phosphate (Pi) were evident on the first day after PDT in all cases. The β-ATP/total phosphate (P) ratio was 0.64 ± 0.29% (average ± s.d.) in complete response, 0.67 ± 0.30% in recurrence and 2.45 ± 0.93% in partial response. Comparison of this ratio to the histological findings revealed that the β-ATP/total P ratio reflects the HeLa cell tumours which survived PDT. In other words, partial response on the one hand was distinguished from complete response and recurrence on the other with this ratio 1 day after PDT (P < 0.05). In addition, the ratio of phosphomonoester (PME) to Pi rose beyond 1.0 when macroscopic recurrence occurred, while it stayed under 1.0 in complete response. This finding suggests that the recurrence of HeLa cell tumours can be detected by the PME/Pi ratio. © 1999 Cancer Research Campaign
Keywords: photodynamic therapy (PDT), phosphorus 31 magnetic resonance spectroscopy (31P MRS), YAG-optical parametric oscillator laser (YAG-OPO laser), ATX-S10, HeLa cell tumour
Full Text
The Full Text of this article is available as a PDF (198.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bremner J. C., Bradley J. K., Stratford I. J., Adams G. E. Magnetic resonance spectroscopic studies on 'real-time' changes in RIF-1 tumour metabolism and blood flow during and after photodynamic therapy. Br J Cancer. 1994 Jun;69(6):1083–1087. doi: 10.1038/bjc.1994.212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Ceckler T. L., Gibson S. L., Kennedy S. D., Hill R., Bryant R. G. Hetergeneous tumour response to photodynamic therapy assessed by in vivo localised 31P NMR spectroscopy. Br J Cancer. 1991 Jun;63(6):916–922. doi: 10.1038/bjc.1991.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Daly P. F., Cohen J. S. Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications: a review. Cancer Res. 1989 Feb 15;49(4):770–779. [PubMed] [Google Scholar]
- Daly P. F., Lyon R. C., Faustino P. J., Cohen J. S. Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy. J Biol Chem. 1987 Nov 5;262(31):14875–14878. [PubMed] [Google Scholar]
- Dewhirst M. W., Sostman H. D., Leopold K. A., Charles H. C., Moore D., Burn R. A., Tucker J. A., Harrelson J. M., Oleson J. R. Soft-tissue sarcomas: MR imaging and MR spectroscopy for prognosis and therapy monitoring. Work in progress. Radiology. 1990 Mar;174(3 Pt 1):847–853. doi: 10.1148/radiology.174.3.2154837. [DOI] [PubMed] [Google Scholar]
- Evanochko W. T., Ng T. C., Glickson J. D., Durant J. R., Corbett T. H. Human tumors as examined by in vivo 31P NMR in athymic mice. Biochem Biophys Res Commun. 1982 Dec 31;109(4):1346–1352. doi: 10.1016/0006-291x(82)91925-8. [DOI] [PubMed] [Google Scholar]
- Fisher A. M., Murphree A. L., Gomer C. J. Clinical and preclinical photodynamic therapy. Lasers Surg Med. 1995;17(1):2–31. doi: 10.1002/lsm.1900170103. [DOI] [PubMed] [Google Scholar]
- 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]
- Gibson S. L., Murant R. S., Hilf R. Photosensitizing effects of hematoporphyrin derivative and photofrin II on the plasma membrane enzymes 5'-nucleotidase, Na+K+-ATPase, and Mg2+-ATPase in R3230AC mammary adenocarcinomas. Cancer Res. 1988 Jun 15;48(12):3360–3366. [PubMed] [Google Scholar]
- Henderson B. W., Dougherty T. J. How does photodynamic therapy work? Photochem Photobiol. 1992 Jan;55(1):145–157. doi: 10.1111/j.1751-1097.1992.tb04222.x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Hua Z., Gibson S. L., Foster T. H., Hilf R. Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. Cancer Res. 1995 Apr 15;55(8):1723–1731. [PubMed] [Google Scholar]
- Kato H. [History of photodynamic therapy--past, present and future]. Gan To Kagaku Ryoho. 1996 Jan;23(1):8–15. [PubMed] [Google Scholar]
- 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]
- 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]
- Negendank W. Studies of human tumors by MRS: a review. NMR Biomed. 1992 Sep-Oct;5(5):303–324. doi: 10.1002/nbm.1940050518. [DOI] [PubMed] [Google Scholar]
- Perlin D. S., Murant R. S., Gibson S. L., Hilf R. Effects of photosensitization by hematoporphyrin derivative on mitochondrial adenosine triphosphatase-mediated proton transport and membrane integrity of R3230AC mammary adenocarcinoma. Cancer Res. 1985 Feb;45(2):653–658. [PubMed] [Google Scholar]
- Steen R. G. Response of solid tumors to chemotherapy monitored by in vivo 31P nuclear magnetic resonance spectroscopy: a review. Cancer Res. 1989 Aug 1;49(15):4075–4085. [PubMed] [Google Scholar]
- Weishaupt K. R., Gomer C. J., Dougherty T. J. Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res. 1976 Jul;36(7 Pt 1):2326–2329. [PubMed] [Google Scholar]
