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Fluorescence localization and kinetics of mTHPC and liposomal formulations of mTHPC in the window-chamber tumor model

Authors

  • Sebastiaan A. H. J. de Visscher,

    Corresponding author
    1. Department of Oral and Maxillofacial Surgery, Division of Oncology, University Medical Center Groningen, The Netherlands
    • Department of Oral and Maxillofacial Surgery, Room S3.214, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
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  • Slávka Kaščáková,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Henriëtte S. de Bruijn,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Angélique van der Ploeg - van den Heuvel,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Arjen Amelink,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Henricus J. C. M. Sterenborg,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Dominic J. Robinson,

    1. Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
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  • Jan L. N. Roodenburg,

    1. Department of Oral and Maxillofacial Surgery, Division of Oncology, University Medical Center Groningen, The Netherlands
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  • Max J. H. Witjes

    1. Department of Oral and Maxillofacial Surgery, Division of Oncology, University Medical Center Groningen, The Netherlands
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Abstract

Background and Objective

Foslip® and Fospeg® are liposomal formulations of the photosensitizer mTHPC, intended for use in Photodynamic Therapy (PDT) of malignancies. Foslip consists of mTHPC encapsulated in conventional liposomes, Fospeg consists of mTHPC encapsulated in pegylated liposomes. Possible differences in tumor fluorescence and vasculature kinetics between Foslip, Fospeg, and Foscan® were studied using the rat window-chamber model.

Material and Methods

In 18 rats a dorsal skin fold window chamber was installed and a mammary carcinoma was transplanted in the subcutaneous tissue. The dosage used for intravenous injection was 0.15 mg/kg mTHPC for each formulation. At seven time-points after injection (5 minutes to 96 hours) fluorescence images were made with a CCD. The achieved mTHPC fluorescence images were corrected for tissue optical properties and autofluorescence by the ratio fluorescence imaging technique of Kascakova et al. Fluorescence intensities of three different regions of interest (ROI) were assessed; tumor tissue, vasculature, and surrounding connective tissue.

Results

The three mTHPC formulations showed marked differences in their fluorescence kinetic profile. After injection, vascular mTHPC fluorescence increased for Foslip and Fospeg but decreased for Foscan. Maximum tumor fluorescence is reached at 8 hours for Fospeg and at 24 hours for Foscan and Foslip with overall higher fluorescence for both liposomal formulations. Foscan showed no significant difference in fluorescence intensity between surrounding tissue and tumor tissue (selectivity). However, Fospeg showed a trend toward tumor selectivity at early time points, while Foslip reached a significant difference (P < 0.05) at these time points.

Conclusions

Our results showed marked differences in fluorescence intensities of Fospeg, Foslip, and Foscan, which suggest overall higher bioavailability for the liposomal formulations. Pegylated liposomes seemed most promising for future application; as Fospeg showed highest tumor fluorescence at the earlier time points. Lasers Surg. Med. 43:528–536, 2011. © 2011 Wiley-Liss, Inc.

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