Potentiation of the Antitumor Effect of Merocyanine 540‐mediated Photodynamic Therapy by Amifostine and Amphotericin B

Abstract

Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that non-cytotoxic concentrations of amifostine (Ethyol, Ethiofos, WR-2721) and amphotericin B used either alone or in combination potentiate the MC540-sensitized photoinactivation of leukemia cells, wildtype small cell lung cancer cells, and cisplatin-resistant small cell lung cancer cells. Amphotericin B also enhances the MC540-sensitized photoinactivation of normal CFU-GM whereas amifostine protects CFU-GM against the cytotoxic action of MC540-PDT. The yield of CD34-positive normal hematopoietic stem and progenitor cells is only minimally diminished by pretreatment with amifostine, amphotericin B, or combinations of amifostine plus amphotericin B. Purging protocols that combine MC540-PDT with amifostine or with amifostine plus amphotericin B may offer a simple and effective approach to the purging of autologous stem cell grafts that are contaminated with solid tumor cells or the purging of stem cell grafts from heavily pretreated leukemia patients that contain reduced numbers of normal stem and progenitor cells and, therefore, can ill afford additional losses caused by purging.

Combination of Photodynamic Therapy with Anti-Cancer Agents

“…A different study on potential combinations was reported by Tsujino and colleagues [66]. They studied the effect of amifosine and/or amphotericin B, drugs usually used concomitantly with chemotherapy, in the anti-tumor effect of MC540-PDT over leukemia cells, wild-type small cell lung cancer cells and cisplatinresistant small cell lung cancer cells.…”

Purging efficacy of ZnPcH1‐based photodynamic therapy on chronic myeloid leukemia bone marrow

“…Photodynamic therapy (PDT) is an effective anticancer modality in which the generation of reactive oxygen species, especially singlet oxygen, can kill cancerous cells. Ex vivo PDT has been proven capable of eliminating the residual tumor cells in auto-HSCT with little side effects (Hrkal, Grebenova & Cajthamlova, 2002;Anderson et al, 2003;Miyagi et al, 2003;Kuzelova et al, 2004;Lee et al, 2004;Zhang & Zhang, 2004;Furre et al, 2005;Huang et al, 2006;Tsujino et al, 2006). Synthetic phthalocyanines are a secondgeneration photosensitizers with strong absorption in the red visible region, high singlet oxygen quantum yield, and low dark toxicity.…”

Hexaminolevulinate-mediated photodynamic purging of leukemia cells from BM

“…[7][8][9][10][11][12][13][14][15][16] Small cell lung, [17][18][19] prostate 19 and breast tumor [19][20][21] cells were mostly analyzed from solid cancers. To mimic in vivo conditions, artificial cell mixture models have been used by several investigators.…”