Pyrene butanol--an efficient, selective and non-metabolized photosensitizing agent for human myeloid leukemia cells.
Methods for ex vivo purging of neoplastic cells from harvested marrow are being developed to increase the efficacy of autologous transplantation. One approach is selective photosensitization, using sensitizing compounds and light radiation. Pyrene-containing fatty acids and lipids are potent photosensitizers, e.g. 12-(1-pyrene)dodecanoic acid (P12), is taken up preferentially by leukemic cells and undergo photoexcitation when exposed to long wave ultra-violet light, resulting in selective killing of leukemic cells. These compounds are incorporated into the neutral- and phospho-lipids of the cells. The presence of intracellular pyrene-linked lipids might present a potential hazard in applying these agents for clinical use. We have, therefore, studied a series of other pyrene-linked compounds with the objective of finding a non-metabolizable photosensitizing agent that can be easily removed from the cells. In the present paper we report the results with pyrene butanol (P4-OH), a pyrene linked short-chain alcohol. When compared to P12, P4-OH was found to be taken up by cells most rapidly and reached saturation within minutes. It did not undergo any metabolism and washing the cells with serum-containing salt solutions removed practically all the P4-OH. This compound was found to be an efficient photosensitizer (in terms of concentrations and time of incubation with the cells) and selective to leukemic cells--it caused a 99% reduction in leukemic clonogenic cells under conditions that normal hemopoietic progenitors remained almost intact. These properties make P4-OH a potential photosensitizer for clinical application.
Fibach
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Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Rabia
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SA
Gatt
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D000208:Acute Disease; D016465:Bone Marrow Purging / Q000379:methods*; D000440:Butanols / Q000493:pharmacokinetics*; D006801:Humans; D007850:Lauric Acids / Q000493:pharmacokinetics*; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011721:Pyrenes / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence; D014407:Tumor Cells, Cultured
D000440:Butanols; D007850:Lauric Acids; D011721:Pyrenes; C040596:12-(1-pyrene)dodecanoic acid