Abstract
Interstitial photodynamic therapy (I-PDT) is a promising therapy considered for patients with locally advanced cancer. In I-PDT, laser fibers are inserted into the tumor for effective illumination and activation of the photosensitizer in a large tumor. The intratumoral light irradiance and fluence are critical parameters that affect the response to I-PDT. In vivo animal models are required to conduct light dose studies, to define optimal irradiance and fluence for I-PDT. Here we describe two animal models with locally advanced tumors that can be used to evaluate the response to I-PDT. One model is the C3H mouse bearing large subcutaneous SCCVII carcinoma (400–600 mm3). Using this murine model, multiple light regimens with one or two optical fibers with cylindrical diffuser ends (cylindrical diffuser fiber, CDF) can be used to study tumor response to I-PDT. However, tissue heating may occur when 630 nm therapeutic light is delivered through CDF at an intensity ≥60 mW/cm and energy ≥100 J/cm. These thermal effects can impact tumor response while treating locally advanced mice tumors. Magnetic resonance imaging and thermometry can be used to study these thermal effects. A larger animal model, New Zealand White rabbit with VX2 carcinoma (~5000 mm3) implanted in either the sternomastoid (neck implantation model) or the biceps femoris muscle (thigh implantation model), can be used to study I-PDT with image-based pretreatment planning using computed tomography. In the VX2 model, the light delivery can include the use of multiple laser fibers to test light dosimetry and delivery that are relevant for clinical use of I-PDT.
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Acknowledgments
The authors would like to thank Diane Filippini for her assistance in obtaining the CT scans and Dr. Craig Hendler MD for conducting the diagnosis of CT scans, at the Department of Radiology at Roswell Park. This work was supported in part by National Cancer Institute of the National Institutes of Health under Award Number R01CA193610 to Gal Shafirstein, and by Roswell Park Comprehensive Cancer Center Support Grant P30CA16056. We thank Concordia Laboratories Inc. for providing the porfimer sodium (Photofrin) at no cost.
The authors would like to thank the staff of the shared resources at Roswell Park Comprehensive Cancer Center for their technical assistance in performing these studies: Laboratory Animal Shared Resource and Translational Imaging Shared Resource. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or Roswell Park Comprehensive Cancer Center.
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Gal Shafirstein, David Bellnier, and Emily Oakley are co-inventors in patent applications (owned by Roswell Park Comprehensive Cancer Center) of a light dosimetry system for interstitial and thermal photodynamic therapy. Gal Shafirstein acknowledges research grant support from Concordia Laboratories Inc. Gal Shafirstein acknowledges a service on the advisory board for Concordia International Corp. and Pinnacle Biologics, Inc. All other co-authors declare no potential conflicts of interest.
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Shafirstein, G. et al. (2022). In Vivo Models for Studying Interstitial Photodynamic Therapy of Locally Advanced Cancer. In: Broekgaarden, M., Zhang, H., Korbelik, M., Hamblin, M.R., Heger, M. (eds) Photodynamic Therapy. Methods in Molecular Biology, vol 2451. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2099-1_11
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DOI: https://doi.org/10.1007/978-1-0716-2099-1_11
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