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Open AccessArticle

Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy

1
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Department of Physics and Astronomy, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1584; https://doi.org/10.3390/cancers12061584
Received: 30 April 2020 / Revised: 30 May 2020 / Accepted: 11 June 2020 / Published: 15 June 2020
(This article belongs to the Section Methods and Technologies Development)
Fluence rate is an effector of photodynamic therapy (PDT) outcome. Lower light fluence rates can conserve tumor perfusion during some illumination protocols for PDT, but then treatment times are proportionally longer to deliver equivalent fluence. Likewise, higher fluence rates can shorten treatment time but may compromise treatment efficacy by inducing blood flow stasis during illumination. We developed blood-flow-informed PDT (BFI-PDT) to balance these effects. BFI-PDT uses real-time noninvasive monitoring of tumor blood flow to inform selection of irradiance, i.e., incident fluence rate, on the treated surface. BFI-PDT thus aims to conserve tumor perfusion during PDT while minimizing treatment time. Pre-clinical studies in murine tumors of radiation-induced fibrosarcoma (RIF) and a mesothelioma cell line (AB12) show that BFI-PDT preserves tumor blood flow during illumination better than standard PDT with continuous light delivery at high irradiance. Compared to standard high irradiance PDT, BFI-PDT maintains better tumor oxygenation during illumination and increases direct tumor cell kill in a manner consistent with known oxygen dependencies in PDT-mediated cytotoxicity. BFI-PDT promotes vascular shutdown after PDT, thereby depriving remaining tumor cells of oxygen and nutrients. Collectively, these benefits of BFI-PDT produce a significantly better therapeutic outcome than standard high irradiance PDT. Moreover, BFI-PDT requires ~40% less time on average to achieve outcomes that are modestly better than those with standard low irradiance treatment. This contribution introduces BFI-PDT as a platform for personalized light delivery in PDT, documents the design of a clinically-relevant instrument, and establishes the benefits of BFI-PDT with respect to treatment outcome and duration. View Full-Text
Keywords: photodynamic therapy; vascular response; Photofrin?; hemodynamic; perfusion; blood flow monitoring; light modulation; diffuse correlation spectroscopy; phosphorescence quenching; Oxyphor photodynamic therapy; vascular response; Photofrin?; hemodynamic; perfusion; blood flow monitoring; light modulation; diffuse correlation spectroscopy; phosphorescence quenching; Oxyphor
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Ong, Y.H.; Miller, J.; Yuan, M.; Chandra, M.; El Khatib, M.; Vinogradov, S.A.; Putt, M.E.; Zhu, T.C.; Cengel, K.A.; Yodh, A.G.; Busch, T.M. Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy. Cancers 2020, 12, 1584.

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