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Targeting of the tumor microcirculation with a new photosensitizer
Author(s): Christoph Abels; Marc Dellian; Rolf-Markus Szeimies; Pia Steinbach; C. Richert; Alwin E. Goetz
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Paper Abstract

Tumors are characterized by an insufficient neoangiogenesis. Therefore targeting of the fragile tumor microcirculation by photodynamic therapy (PDT) may induce easily tumor ischemia leading to tumor necrosis. Nine-acetoxy-2,7,12,17-tetrakis-((beta) -methoxyethyl)- prophycene (ATMPn) is a chemically pure, lipophilic substance and revealed superior photodynamic characteristics in vitro as compared to PhotofrinR. In this study pharmacokinetics, photodynamic effects and localization of ATMPn incorporated in small unilamellar liposomes in tumor and surrounding normal tissue were evaluated. Amelanotic melanomas (A-Mel-3) were implanted in dorsal skin fold chambers fitted to Syrian Golden hamsters (70 - 80 g b.w.). Fluorescence kinetics of ATMPn administered intravenously (1.4 micrometers ol/kg b.w.; n equals 8) were monitored by intravital microscopy. Quantitative measurements of fluorescence intensity were carried out by digital image analysis. For tumor growth studies 1.4 micrometers ol/kg was injected 24 h (n equals 3), 3 h (n equals 3), 1 min (n equals 6) and 2.8 micrometers ol/kg 1 min (n equals 6) before PDT (630 nm, 100 mW/cm2, 100 J/cm2). Tumor growth was measured over 28 days. Solid tumors (n equals 3) were excised 1 min after injection of ATMPn (1.4 micrometers ol/kg) and cryostat sections (10 micrometers) were analyzed by confocal laser scanning microscopy (CSLM) to determine tissue localization of dye. Maximal fluorescence (mean plus or minus S.E.) arose in tumor (94 plus or minus 7%) and surrounding host tissue (67 plus or minus 5%) 30 s post injection followed by a rapid decrease. Hardly any fluorescence was detectable after 12 h. Only PDT 1 min after injection of ATMPn was effective yielding 1/6 complete remission (1.4 micrometers ol/kg) and 3/6 complete remissions (2.8 mmol/kg), respectively. At that time dye is primarily localized in vessels and vessel walls as shown by CSLM. ATMPn in liposomes reveals very rapid kinetics thus suitable for intraoperative PDT. Moreover, PDT (2.8 micrometers ol/kg) at time, when dye is localized in tumor microcirculation, exhibits best tumor killing effects.

Paper Details

Date Published: 31 January 1996
PDF: 6 pages
Proc. SPIE 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities, (31 January 1996); doi: 10.1117/12.230983
Show Author Affiliations
Christoph Abels, Ludwig-Maximilians-Univ. (Germany)
Marc Dellian, Ludwig-Maximilians-Univ. (Germany)
Rolf-Markus Szeimies, Univ. Regensburg (Germany)
Pia Steinbach, Univ. Regensburg (Germany)
C. Richert, Swiss Federal Insititute of Technology (Switzerland)
Alwin E. Goetz, Ludwig-Maximilians-Univ. Muenchen (Germany)

Published in SPIE Proceedings Vol. 2625:
Photochemotherapy: Photodynamic Therapy and Other Modalities
Benjamin Ehrenberg; Giulio Jori; Johan Moan, Editor(s)

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