Mr. Dayton D. McMillan Profile

Dayton D. McMillan

at Colorado State Univ

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Proceedings Article | 14 April 2014 Paper

Comparison of singlet oxygen threshold dose for PDT

Timothy Zhu, Baochang Liu, Michele Kim, Dayton McMillan, Xing Liang, Jarod Finlay, Theresa Busch

Proceedings Volume 8931, 89310I (2014) https://doi.org/10.1117/12.2039719

KEYWORDS: Oxygen, Photodynamic therapy, In vivo imaging, Tumors, Picosecond phenomena, Tissue optics, Molecules, In vitro testing, Absorption, Tissues

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Macroscopic modeling of singlet oxygen (¹O₂) is of particular interest because it is the major cytotoxic agent causing biological effects for type II photosensitizers during PDT. We have developed a macroscopic model to calculate reacted singlet oxygen concentration ([1O2]_rx for PDT. An in-vivo RIF tumor mouse model is used to correlate the necrosis depth to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include 4 photosensitizer specific photochemical parameters along with the apparent singlet oxygen threshold concentration. Photosensitizer specific model parameters are determined for several type II photosensitizers (Photofrin, BPD, and HPPH). The singlet oxygen threshold concentration is approximately 0.41 - 0.56 mM for all three photosensitizers studied, assuming that the fraction of singlet oxygen generated that interacts with the cell is (f = 1). In comparison, value derived from other in-vivo mice studies is 0.4 mM for mTHPC. However, the singlet oxygen threshold doses were reported to be 7.9 and 12.1 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC and Photofrin PDT, respectively. The sensitivity of threshold singlet oxygen dose for our experiment is examined. The possible influence of vascular vs. apoptotic cell killing mechanism on the singlet oxygen threshold dose is discussed using the BPD with different drug-light intervals 3 hrs vs. 15 min. The observed discrepancies between different experiments warrant further investigation to explain the cause of the difference.

Proceedings Article | 13 March 2013 Paper

Parameter determination for singlet oxygen modeling of BPD-mediated PDT

Dayton McMillan, Daniel Chen, Michele Kim, Xing Liang, Timothy Zhu

Proceedings Volume 8568, 856810 (2013) https://doi.org/10.1117/12.2003277

KEYWORDS: Photodynamic therapy, Tumors, Oxygen, Tissue optics, Light sources, Data modeling, Ions, Neodymium, Cancer, Oncology

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Photodynamic therapy (PDT) offers a cancer treatment modality capable of providing minimally invasive localized tumor necrosis. To accurately predict PDT treatment outcome based on pre-treatment patient specific parameters, an explicit dosimetry model is used to calculate apparent reacted ¹O₂ concentration ([¹O₂]rx) at varied radial distances from the activating light source inserted into tumor tissue and apparent singlet oxygen threshold concentration for necrosis ([¹O2]_rx, sd) for type-II PDT photosensitizers. Inputs into the model include a number of photosensitizer independent parameters as well as photosensitizer specific photochemical parameters ξ σ, and β. To determine the specific photochemical parameters of benzoporphyrin derivative monoacid A (BPD), mice were treated with BPDPDT with varied light source strengths and treatment times. All photosensitizer independent inputs were assessed pre-treatment and average necrotic radius in treated tissue was determined post-treatment. Using the explicit dosimetry model, BPD specific ξ σ, and β photochemical parameters were determined which estimated necrotic radii similar to those observed in initial BPD-PDT treated mice using an optimization algorithm that minimizes the difference between the model and that of the measurements. Photochemical parameters for BPD are compared with those of other known photosensitizers, such as Photofrin. The determination of these BPD specific photochemical parameters provides necessary data for predictive treatment outcome in clinical BPD-PDT using the explicit dosimetry model.

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