Author: David Alcorta, Joseph Farina, Timothy Haystead, Philip Hughes, Keshav Jha, Mark Oldham, Victoria J. P. Radosova 👨🔬
Affiliation: Duke University Department of Pharmacology and Cancer Biology, Medical Physics Graduate Program, Duke University, Duke University Department of Medicine, Duke University, Duke University Pharmacology and Cancer Biology, Department of Radiation Oncology, Duke University Medical Center 🌍
Purpose: This study attempts to simulate the activation of targeted photodynamic molecules using visible laser light and characterize the direct Reactive Oxygen Species (ROS) generated by Cherenkov and laser radiation for prostate and breast cancer.
Methods: HS583, a novel photodynamic molecule made of an HSP90 inhibitor bound to verteporfin, was manufactured in house. Optical properties of HS583 were characterized using a Shimadzu UV-3600i spectrophotometer and an Edinburgh Instruments fluorometer. A TOPAS Monte Carlo simulation was created to model HS583 photoactivation under visible light. Beam sources at wavelengths matching HS583 absorption peaks were simulated on a polypropylene vial filled with water. A 0.1 µL scoring phantom within the vial was divided into 50 nm voxels with 1 µM of HS583 randomly distributed. Photon fluence, energy absorbed by HS583, and fluorescence of 10 million photons were scored for the molecule for each wavelength and compared to the biological effect of HS583 in cells when exposed to light. Data was adjusted to a 1 J/cm^2 beam and analyzed in Python.
Results: Absorption measurements confirmed a maximum absorption peak of HS583 at 425 nm, with smaller peaks at 688, 620, and 575 nm, and a single emission peak at 700 nm. Simulations demonstrated that for a 1 J/cm^2 incident beam, 6.1E12±0.23E12 eV is absorbed at 688 nm, 1.4E12±0.10E12 eV at 620 nm, 3.4E12±0.95E12 eV at 575 nm, and 2.1E13±0.83E12 nm at 425. Assuming an energy required to hydrolyze water of 1.23 eV, this corresponds to 1.1E-11±0.04E-11 moles ROS generated.
Conclusion: The photodynamic molecules created in the Haystead laboratory create ROS when exposed to visible laser light. This simulation provides a way to estimate ROS created in a controlled environment, which can be notoriously difficult to measure experimentally.