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Use of 5-Aminolevulinic Acid Esters to Improve Photodynamic Therapy on Cells in Culture¹

Laboratory of Photobiology, National Museum of Natural History, INSERM U.312, 43 rue Cuvier, 75231 Paris Cedex 05, France [J-M. G.], and Institute for Cancer Research, Department of Biophysics, Montebello, N-0310 Oslo, Norway [K. B., Q. P., H. A., P. K. S., L-W. M., J. M.]

Human tumor cells of the lines WiDr (adenocarcinoma of the rectosigmoid colon), NHIK 3025 (carcinoma of the cervix), and V79 Chinese hamster fibroblasts were treated with 5-aminolevulinic acid (ALA) and ALA esterified to C₁–C₃ and C₆–C₈ chained aliphatic alcohols (ALA-esters). In the human cell lines, esterification of ALA with the long-chain (C₆–C₈) alcohols was found to reduce 30–150-fold the amount of ALA needed to reach the same level of protoporphyrin IX (PpIX) accumulation as with non-esterified ALA. The long-chained ALA-esters were less efficient in stimulating PpIX formation in V79 cells, i.e., the same amount of PpIX was formed by a 1–2.6-fold lower concentration of long-chained ALA-esters than with ALA. Short-chained ALA-esters (C₁–C₃) induced 5 to 10 times lower PpIX accumulation than ALA in all of the cell lines. High-performance liquid chromatography and fluorescence microscopic studies indicated that esterification of ALA has neither impact on the fluorescing porphyrin species formed nor impact on their intracellular localization. The PpIX formed from ALA-esters and ALA was found to be equally efficient in sensitizing cells to photoinactivation. The present results indicate that esterified ALAs are new and promising drugs for use in photochemotherapy of cancer.

¹ This work was supported by the Research Council of Norway (NFR) and by the National Institute of Health and Medical Research (INSERM), as part of a researchers' exchange program between Norway and France. It has also been supported by the Commission of the European Communities through the program "Human Capital and Mobility Programme" (PDT Euronet).

² Visiting scientist in Oslo.

³ To whom requests for reprints should be addressed. Phone: 47 22 93 42 60; Fax: 47 22 93 42 70; E-mail: kristian.berg@labmed.uio.no.

Received 7/18/96. Accepted 2/14/97.

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