Premium
ACTIVATION OF BENZOPORPHYRIN DERIVATIVE IN THE CIRCULATION OF MICE WITHOUT SKIN PHOTOSENSITIVITY
Author(s) -
Richter Anna M.,
Jain Ashok K.,
Obochi Modestus,
Meadows Howard,
Canaan Alice J.,
Levy Julia G.
Publication year - 1994
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1994.tb05046.x
Subject(s) - phototoxicity , photosensitivity , photosensitizer , clonogenic assay , in vitro , chemistry , medicine , photodynamic therapy , cytotoxicity , endocrinology , biochemistry , materials science , optoelectronics , organic chemistry
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/cm 2 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 μg/mL. The light treatment resulted in between 70 and 80% photoinactivation of circulating BPD. When LI 210 tumor cells were preincubated with BPD and injected i.v. into mice immediately before total‐body light treatment (160 J/cm 2 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. Thus, activation of this photosensitizer in the circulation can be achieved by transdermal light exposure without causing skin photosensitivity provided that light exposure is performed at a time when the first phase of plasma clearance is complete and when the drug has not yet accumulated in skin.