Increasing the effect of photodynamic therapy on the RIF-1 murine sarcoma, using the bioreductive drugs RSU1069 and RB6145.
The effect of combining photodynamic therapy (PDT) and bioreductive drugs has been investigated using the RIF-1 experimental murine tumour. Light was delivered interstially to the tumour at 675 nm using a single optical fibre attached to an argon-ion dye laser. The photosensitizer was disulphonated aluminium phthalocyanine (AlS2Pc) and the bioreductive drugs were the dual function nitroimidazole RSU1069 and its pro-drug RB6145. Varying the time between administration of the photosensitizer and light delivery (TL) from 30 min to 24 h had little influence on the extent of the anti-tumour effect of PDT alone, as measured by the regrowth delay endpoint. When the bioreductive drug was included in the treatment, administered 20 min before light irradiation, regrowth delay was greatly increased. The effectiveness of the combined treatment was optimum for short values of TL (about 1 h). Fluorescence microscopy was used to investigate the distribution of the photosensitizer within the tumours. This showed that the compound was mainly confined to the tumour vasculature over the first few hours post-treatment. The high efficacy of the combined treatment of PDT and bioreductive drugs for short values of TL suggest that photodynamic action, during the period when the photosensitizer AlS2Pc is confined to the vasculature, enhances the severity of tumour hypoxia which is sufficient to induce activation of the bioreductive drugs.
Bremner
J C
JC
MRC Radiobiology Unit, Chilton, UK.
Adams
G E
GE
Pearson
J K
JK
Sansom
J M
JM
Stratford
I J
IJ
Bedwell
J
J
Bown
S G
SG
MacRobert
A J
AJ
Phillips
D
D
D000818:Animals; D007211:Indoles / Q000627:therapeutic use; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009593:Nitroimidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D012509:Sarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007211:Indoles; D009593:Nitroimidazoles; D009942:Organometallic Compounds; C067834:RB 6145; C060570:aluminum phthalocyanine; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole