Cell and tissue responses of a murine tumour to phthalocyanine-mediated photodynamic therapy.
Mice bearing a subcutaneously growing tumour (Colo 26) were injected intravenously with the photosensitiser chloroaluminum sulphonated phthalocyanine (5 mg/kg) 24 h prior to irradiating the tumour with laser light (675 nm; 50mW, 100 J/tumour). Energy status of the tumour, as assessed by the loss of high energy phosphates in the 31P-nuclear magnetic resonance spectra, was altered dramatically following treatment, such that the ATP fell to undetectable levels within 1 h of light irradiation. However, assessment of the clonogenic capacity of neoplastic cells isolated from dissociated tumours showed that these rapid changes in cellular metabolism were not reflected in similar rapid changes in cell viability. Reductions in clonogenic capacity, which fell to less than 0.1% of control values at 24h postirradiation, closely mirrored those resulting from the cessation of vascular perfusion. Evaluation of tumour blood flow, using the technique of hydrogen washout, showed that the treatment protocol evoked a gradual and selective reduction in flow within the tumour resulting in complete vascular stasis by approximately 5 h after treatment. The results indicate that while chloroaluminum sulphonated phthalocyanine-mediated photodynamic therapy caused early metabolic damage in neoplastic cells, loss of viability paralleled the induction of complete inhibition of vascular flow in the tumour.
van Bruggen
N
N
Department of Biophysics, Hunterian Institute, Royal College of Surgeons of England, Lincoln's Inn Fields, London, U.K.
Chan
W S
WS
Syha
J
J
Marshall
J F
JF
Proctor
E
E
Williams
S R
SR
Gadian
D G
DG
Hart
I R
IR
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D007211:Indoles / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D007211:Indoles; D009942:Organometallic Compounds; D011838:Radiation-Sensitizing Agents; C044797:chloroaluminum phthalocyanine