Activation of Benzoporphyrin Derivative in the Circulation of Mice Without Skin Photosensitivity

Abstract

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)

IL-10 Contributes to the Inhibition of Contact Hypersensitivity in Mice Treated with Photodynamic Therapy

“…Our laboratory has evaluated PDT using the photosensitizer verteporfin in a number of immunologic test systems (8,10). Prolonged skin allograft acceptance (13), impaired adoptive transfer of autoimmune encephalomyelitis (26), prevention of adjuvant-enhanced arthritis (27), and inhibition of CHS (14) have been described for verteporfin-mediated PDT.…”

New Applications in Photodynamic Therapy Introduction

“…In our laboratory, working with BPD, we observed that this photosensitizer could be activated (photobleached) in the circulation of mice if they were exposed to whole body illumination with red light under conditions that produced no observable skin photosensitivity. This procedure was termed transcutaneous PDT (15). Since then a number of studies have been undertaken to determine whether this "low level PDT" effect could influence immunological responsiveness with the thought that this could be a novel approach to the treatment of autoimmune diseases.…”

Photodynamic therapy; a comparison with other immunomodulatory treatments of adjuvant-enhanced arthritis in MRL-lpr mice

“…Whole body transcutaneous photodynamic therapy was administered to unshaved miee with 80 J/em' light dose applied on day 0, 10, and 20 after arthritis induction. The optimal concentration of BPD and light dose necessary for cell killing was determined in preliminary studies [27].…”

“…Studies with this phoiosensitizer have shown lhat it is taken up selectively by activated lymphocytes (those bearing either the IL-2 receptor (IL-2R) or high levels of HLA-DR antigen) or other highly proliferative cells, thus rendering these populations susceptible to photodynamic destruction wilh 690-nm light [26]. Further, in recent experiments we demonstrated that BPD eotild be activated transdermally while in the circulation by exposure of animals to whole body illumination with red light [27]. These treatments resulted in photoactivation of between SQ% and 70% of circulating BPD.…”