Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy
Open Access
- 15 June 2020
- Vol. 12 (6), 1584
- https://doi.org/10.3390/cancers12061584
Abstract
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.Funding Information
- National Institutes of Health (R01 CA085831, P01 CA087971, R01 CA236362, R01 NS060653, P41 EB015893)
This publication has 60 references indexed in Scilit:
- Photodynamic Therapy (PDT): PDT MechanismsClinical Endoscopy, 2013
- Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic TherapyPLOS ONE, 2012
- Tumor Vascular Microenvironment Determines Responsiveness to Photodynamic TherapyCancer Research, 2012
- Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation deliveryBiomedical Optics Express, 2012
- Two New “Protected” Oxyphors for Biological Oximetry: Properties and Application in Tumor ImagingAnalytical Chemistry, 2011
- Stimulation of anti-tumor immunity by photodynamic therapyExpert Review of Clinical Immunology, 2011
- Monitoring blood flow responses during topical ALA-PDTBiomedical Optics Express, 2010
- Increasing Damage to Tumor Blood Vessels during Motexafin Lutetium-PDT through Use of Low Fluence RateRadiation Research, 2010
- Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapyPhotochemical & Photobiological Sciences, 2009
- Light Delivery over Extended Time Periods Enhances the Effectiveness of Photodynamic TherapyClinical Cancer Research, 2008