Abstract
Photodynamic therapy (PDT) is a developing approach to the treatment of solid tumours which requires the combined action of light and a photosensitizing drug in the presence of adequate levels of molecular oxygen. We have developed a novel series of photosensitizers based on zinc phthalocyanine which are water-soluble and contain neutral (TDEPC), positive (PPC) and negative (TCPC) side-chains. The PDT effects of these sensitizers have been studied in a mouse model bearing the RIF-1 murine fibrosarcoma line studying tumour regrowth delay, phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the study were to determine if MRS measurements made at the time of PDT treatment could potentially be predictive of ultimate PDT efficacy and to assess the effects of sensitizer charge on PDT in this model. It was clearly demonstrated that there is a relationship between MRS measurements during and immediately following PDT and the ultimate effect on the tumour. For all three drugs, tumour regrowth delay was greater with a 1-h time interval between drug and light administration than with a 24-h interval. In both cases, the order of tumour regrowth delay was PPC > TDEPC = TCPC (though the data at 24 h were not statistically significant). Correspondingly, there were greater effects on phosphate metabolism (measured at the time of PDT or soon after) for the 1-h than for the 24-h time interval. Again effects were greatest with the cationic PPC, with the sequence being PPC > TDEPC > TCPC. A parallel sequence was observed for the blood flow effects, demonstrating that reduction in blood flow is an important factor in PDT with these sensitizers.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Bellnier, DA & Henderson, BW (1992) Determinants for photodynamic tissue destruction. In:Photodynamic Therapy: Principles and Clinical Applications, Henderson BW, Dougherty TJ (eds) Marcel Dekker: New York 117–127
Ben-Hur, E (1992) Basic photobiology and mechanisms of action of phthalocyanines. In:Photodynamic Therapy: Basic Principles and Clinical Applications, Henderson BW, Dougherty TJ Marcel Dekker: New York 63–78
Ben-Hur, E, Green, M, Prager, A, Kol, R & Rosenthal, I (1987) Phthalocyanine photosensitization of mammalian cells: biochemical and ultrastructure effects. Photochem Photobiol 46: 651–656
Bradley, JK, Counsell, CJR, Bremner, JCM, Sansom, JM & Adams, GE (1994) The accuracy and reproducibility of measuring blood flow in murine tumours by the D2O uptake and clearance techniques. NMR Biomed 7: 141–148
Bremner, JCM, Counsell, CJR, Adams, GE, Stratford, IJ, Wood, PJ, Dunn, JF & Radda, GK (1991) In vivo 31P muclear magnetic resonance spectroscopy of experimental murine tumours and human tumour xenografts: effects of blood flow modification. Br J Cancer 64: 862–866
Bremner, JCM, Bradley, JK, Stratford, IJ & Adams, GE (1994) Magnetic resonance spectroscopic studies on ‘real-time’ changes in the RIF-1 tumour metabolism and blood flow during and after photodynamic therapy. Br J Cancer 69: 1083–1087
Ceckler, TL, Bryant, RG, Penney, DP, Gibson, SL & Hilf, R (1986) 31P NMR spectroscopy demonstrates decreased ATP levels in vivo as an early response to PDT. Biochem Biophys Res Commun 140: 273–279
Chapman, JD, McPhee, MS, Walz, N, Chetner, MP, Stobbe, CC, Soderlind, K, Arnfield, M, Meeker, BE, Trimble, L & Allen, PS (1991) Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors. J Natl Cancer Inst 83: 1651–1659
Chopp, M, Farmer, H, Hetzel, FW & Schaap, AP (1987) In vivo 31P NMR spectroscopy of mammary carcinoma subjected to subcurative photodynamic therapy. Photochem Photobiol 45: 819–821
Cruse-Sawyer, JE, Griffiths, J, Dixon, B & Brown, SB (1998) The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines. Br J Cancer 77: 965–972
Dougherty, TJ (1993) Photodynamic therapy. Photochem Photobiol 58: 895–900
Fingar, VH, Wieman, TJ, Karavolos, PS, Doak, KW, Ouellet, R & van Lier, JE (1993) The effects of PDT using differently substituted zinc phthalocyanines on vessel constriction, leakage and tumour response. Photochem Photobiol 58: 251–258
Fingar, VH, Wieman, TJ, Karavolos, PS, Doak, KW, Ouellet, R & van Lier, JE (1993) The effects of PDT using differently substituted zinc phthalocyanines on vessel constriction, leakage and tumour response. Photochem Photobiol 58: 251–258
Griffiths, J, Cruse-Sawyer, J, Wood, SR, Schofield, J, Brown, SB & Dixon, B (1994) On the photodynamic therapy action spectrum of zinc phthalocyanine tetrasulphonic acid in vivo. J Photochem Photobiol, B24: 195–199
Griffiths, J, Schofield, J, Wainwright, M & Brown, SB (1997) Some observations on the synthesis of polysubstituted zinc phthalocyanine sensitisers for photodynamic therapy. Dyes Pigments 33: 65–78
Hilf, R, Gibson, SL, Penny, DP, Ceckler, TL & Bryant, RG (1987) Early biochemical responses to photodynamic therapy monitored by NMR spectroscopy. Photochem Photobiol 46: 809–817
Mattiello, J, Eveloch, JL, Brown, E, Schaap, AP & Hetzel, FW (1990) Effect of photodynamic therapy on RIF-1 tumour metabolism and blood flow examined by 31P and 2H NMR spectroscopy. NMR Biomed 3: 64–70
Spikes, JD (1986) Phthalocyanines as photosensitizers in biological systems and for the photodynamic therapy of tumours. Photochem Photobiol 43: 691–699
Stranadko, EF, Skobelkin, OK, Litwin, GD & Astrakhankina, TA (1996). Proc SPIE 2728: 194–205
Stratford, IJ, Adams, GE, Godden, J & Howells, N (1988) Potentiation of the anti-tumour effect of melphalan by the vaso-active drug, hydralazine. Br J Cancer 58: 122–127
Twentyman, PR, Brown, JM, Gray, JW, Franko, AJ, Scoles, MA & Kaleman, RF (1980) A new mouse tumour model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst 64: 595–604
Wood, SR, Holroyd, JA & Brown, SB (1997) The subcellular localisation of Zn(II) phthalocyanines and their redistribution on exposure to light. Photochem Photobiol 65: 397–402
Author information
Authors and Affiliations
Additional information
This paper was prepared with the full participation of Professor GE Adams, before his death on 6 June 1998.
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Bremner, J., Wood, S., Bradley, J. et al. 31P magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines. Br J Cancer 81, 616–621 (1999). https://doi.org/10.1038/sj.bjc.6690738
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690738
Keywords
This article is cited by
-
Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment
British Journal of Cancer (2003)