Activation of benzoporphyrin derivative in the circulation of mice without skin photosensitivity.
In vitro experiments with benzoporphyrin derivative monoacid ring A (BPD) confirmed earlier studies that it was taken up rapidly (within 30 min) to maximum concentrations by all cells tested. It was also confirmed that rapidly dividing tumor cell lines and mitogen-activated murine T lymphocytes took up significantly more (5-10-fold) BPD than did normal splenic lymphocytes. Further experiments were undertaken to determine whether BPD could be activated by whole-body irradiation with red light in the blood of animals, shortly after intravenous (i.v.) administration, in the absence of skin photosensitivity. It was found that shaved and depilated mice injected i.v. 60 min earlier with BPD at between 0.5 and 1.0 mg/kg could tolerate 160 J/cm2 of broad-band red light (560-900 nm) delivered, at a relatively low rate, over a 90 min time interval without developing skin photosensitivity or general phototoxicity. During the treatment time, plasma levels of BPD were between 0.7 and 1.0 micrograms/mL. The light treatment resulted in between 70 and 80% photoinactivation of circulating BPD. When L1210 tumor cells were preincubated with BPD and injected i.v. into mice immediately before total-body light treatment (160 J/cm2 of 590-900 nm light delivered over 90 min), significant reductions in circulating clonogenic tumor cells were observed in blood samples taken immediately following treatment. This indicated that sufficient light was being delivered to BPD in the blood flowing in the peripheral vasculature to effect cytotoxicity to cells containing the photosensitizer without causing either vascular or skin photosensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Richter
A M
AM
Quadra Logic Technologies Inc., Vancouver, British Columbia, Canada.
Jain
A K
AK
Obochi
M
M
Meadows
H
H
Canaan
A J
AJ
Levy
J G
JG
D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010778:Photochemotherapy / Q000379:methods; D011166:Porphyrins / Q000097:blood* / Q000493:pharmacokinetics / Q000528:radiation effects*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011166:Porphyrins; C504224:benzoporphyrin D