Radionuclide Mediated Stimulation of Photodynamic Agents for Precision Phototherapy
Nalinikanth Kotagiri, MD, PhD
James L. Winkle College of Pharmacy, University of Cincinnati, OH, USA
kotaginh@ucmail.uc.edu
Abstract
The management of aggressive malignancies often include combination treatment strategies to achieve optimal cell killing. Several chemotherapeutic drugs are a substantial part of many multimodal treatment schedules for metastatic cancers that includes radiotherapy. Thus, the risk of parallel use of both radiotherapy and drug usage is high due to accidental overlap of radiation-drug interactions. Concomitant chemotherapy and radiation therapy is an established treatment regimen for many neoplasms. For example, paclitaxel (Taxol) has been shown to be antiangiogenic and it also has been shown to enhance the therapeutic effects of ionizing radiation in clinical trials. Therefore, there is a need for systematic examination of drug-radiation interactions and more fundamentally, photochemical and biological interactions between different classes of drugs and radiation. In this study, we screened various FDA approved drugs and evaluated their synergy with different types of radiation sources to determine drugs that exhibit significantly higher toxicity against cancer cells in combination with radiation. Previous studies have explored how energy from radionuclides can be harnessed by certain compounds and nanoparticles for photoactivated therapy. In this study we demonstrate how several FDA approved drugs can potentially be used synergistically with radionuclides for enhanced cancer therapy. Moreover, we also demonstrate how diagnostic radionuclides, such as 18FDG, through ionizing photons, can be repurposed as a radiotherapeutic after cell “priming” by radiosensitizers.
Short Bio
Nalinikanth Kotagiri is an Assistant Professor of Pharmaceutical Sciences in the College of Pharmacy at University of Cincinnati. After training as a Medical Doctor in Andhra Medical College, India, he received his Ph.D in Cell & Molecular Biology from the University of Arkansas. He then worked as a Postdoctoral Fellow in the Mallinckrodt Institute of Radiology at Washington University School of Medicine in St. Louis. He has developed novel optical-nuclear probes for molecular imaging and site-selective activation of therapeutic events. He pioneered the development and use of a clinically translatable depth- and oxygen-independent phototherapy platform using radiopharmaceuticals. His work is published in high-impact journals such as Nature Nanotechnology, Nature Communications and Angewandte Chemie. He has received several research awards including the Dan Bugher Thinking Outside the Box Award and has one granted and two pending patents. He has served as Award Committee co-Chair for the IEEE-Nanomed 2019.