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Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization

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Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization Chem. Rev. 2010, 110, 2795–2838 2795 Imaging and Photodynamic Therapy: Mechanisms, Monitoring, and Optimization Jonathan P. Celli,† Bryan Q. Spring,† Imran Rizvi,†,‡ Conor L. Evans,† Kimberley S. Samkoe,‡ Sarika Verma,† Brian W. Pogue,†,‡ and Tayyaba Hasan*,† Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755 Received September 4, 2009 Contents 4.5. Optical Coherence Tomography in 2819 Photodynamic Therapy 1. Introduction 2795 4.5.1. Optical Coherence Tomography Background 2819 1.1. Photodynamic Therapy and Imaging 2795 4.5.2. Noninvasive Visualization of Photodynamic 2819 1.2. Photochemical and Photophysical Basis of 2799 Therapy in Ophthalmology Photodynamic Therapy and Related Imaging 4.5.3. Doppler Optical Coherence Tomography 2820 2. Imaging of Photosensitizer Fluorescence for 2800 Monitors the Vascular Response to Photo- Detection of Disease and Optimization of dynamic Therapy Surgical Resection 4.5.4. In Vitro Model Treatment Response Imag- 2820 2.1. Overview of Photosensitizer Fluorescence 2800 ing with Optical Coherence Tomography Detection 5. Molecular Imaging of Dynamic Molecular Mecha- 2821 2.2. Early PS Fluorescence Studies 2801 nisms Induced by PDT 2.3. δ-Aminolevulinic Acid-Induced Protoporphyrin IX 2802 5.1. Overview 2821 2.4. Photosensitizer Fluorescence Detection for 2804 5.2. Imaging Molecular Pathways Involved in PDT- 2822 Disease-Specific Applications Induced Apoptosis 2.4.1. Bladder Cancer 2804 5.2.1. Green Fluorescent Protein Sensors for 2822 2.4.2. Brain Cancer 2804 Visualizing Proapoptotic Factor Activation 2.4.3. Ovarian Cancer 2807 and Trafficking 2.4.4. Photosensitizer Fluorescence Detection in 2808 5.2.2. Caspase-Activated Fluorescent Reporter of 2823 Skin Cancer Apoptosis 2.4.5. Photosensitizer Fluorescence Detection in 2810 5.3. Imaging Biomarkers of Therapeutic Responses 2824 Oral Cancer to PDT 2.4.6. Other Applications of Photosensitizer 2810 5.3.1. Heat Shock Protein 70 2824 Fluorescence Detection 5.3.2. Matrix Metalloproteinase 2825 2.5. Perspective and Future Outlook for PFD 2811 5.3.3. Vascular Endothelial Growth Factor 2825 3. Targeted Photosensitizers as Selective 2811 5.4. PET and MRI for Molecular Imaging of Biologi- 2827 Therapeutic and Imaging Agents cal Responses to PDT 3.1. Overview 2811 5.5. Summary of Molecular Imaging To Elucidate 2828 3.2. Site-Specific Delivery 2811 Biological Mechanisms Induced by PDT 3.3. Site-Activated Constructs 2813 6. Perspective and Future Directions 2828 4. Imaging for Planning, Assessment, and Monitoring 2815 6.1. In Vivo Tracking of Cell Migration in Response 2829 Downloaded via UNIV OF NORTH CAROLINA on September 21, 2018 at 13:08:54 (UTC). of Photodynamic Therapy Response to Photodynamic Therapy See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. 4.1. Imaging Methods for Optimization and 2815 6.2. Multiphoton Excitation for Deep Tissue Imaging 2831 Dosimetry of Photodynamic Therapy 6.3. Monitoring Molecular Oxygen for 2831 4.2. Online Monitoring of Photodynamic Therapy 2815 Photodynamic Therapy Dosimetry Response 7. List of Abbreviations 2832 4.3. Imaging Techniques for Assessment of the 2816 8. Acknowledgments 2833 Photodynamic Therapy Outcome 9. References 2833 4.4. Monitoring Oxygen and Dose Rate Effects in 2817 PDT 1. Introduction 4.4.1. Oxygen Measurement 2817 4.4.2. Dose Rate Effects upon the Outcome 2818 1.1. Photodynamic Therapy and Imaging 4.4.3. Vascular Response and Tissue Oxygen 2818 The purpose of this review is to present the current state of the role of imaging in photodynamic therapy (PDT). For * To whom correspondence should be addressed. E-mail: thasan@ the reader to fully appreciate the context of the discussions partners.org. † Massachusetts General Hospital and Harvard Medical School. embodied in this paper we begin with an overview of the ‡ Dartmouth College. PDT process, starting with a brief historical perspective 10.1021/cr900300p 2010 American Chemical Society Published on Web 03/30/2010 2796 Chemical Reviews, 2010, Vol. 110, No. 5 Celli et al. Jonathan Celli is a postdoctoral fellow in the laboratory of Dr. Tayyaba Imran Rizvi is a Doctoral Candidate at the Thayer School of Engineering Hasan at the Wellman Center for Photomedicine at Massachusetts General at Dartmouth College and a Graduate Research Fellow at the Wellman Hospital and Harvard Medical School. He received his B.S. in Physics Center for Photomedicine at Massachusetts General Hospital. His thesis from the University of Massachusetts (2002) and his Ph.D. in Physics research, co-advised by Professors Tayyaba Hasan and Brian Pogue, from Boston University (2007). There, under the mentorship of Professors draws on concepts from tissue engineering and tumor biology to create Shyamsunder Erramilli and Rama Bansil, he studied the pH-dependent in vitro 3D models for human tumors that can be used to design and rheology and microrheology of gastric mucin and motility of the ulcer- evaluate PDT-based combination regimens for cancer. Imran received a causing bacterium Helicobacter pylori. In his current research, he draws B.A. in Natural SciencessBiology from Johns Hopkins University (1997) upon his training in microscopy and quantitative imaging to study PDT and an M.S. in Tumor Biology from Georgetown University (2003). treatment response in pancreatic and ovarian tumor models toward the goal of designing combination treatments to enhance outcomes. Conor Evans received his B.S. in chemical physics from Brown University in 2002 and completed his Ph.D. in physical chemistry in 2007 at Harvard Bryan Quilty Spring is a postdoctoral fellow in the Wellman Center for University under the instruction of Prof. X. Sunney Xie. He worked on Photomedicine at Massachusetts General Hospital and Harvard Medical coherent anti-Stokes Raman scattering (CARS) microscopy during his School. He received a B.S. in Physics from Iowa State University in 2002 doctoral work and became fascinated in applying advanced imaging and a Ph.D. in Biophysics and Computational Biology from the University approaches for solving critical problems in cancer. He moved to the of Illinois at UrbanasChampaign in 2008. His doctoral work with Robert Wellman Center for Photomedicine at Massachusetts General Hospital M. Clegg focused on developing video-rate fluorescence lifetime imaging and joined the groups of Drs. Tayyaba Hasan and Johannes de Boer to and quantitative measurements of Fo¨rster resonance energy transfer. Since pursue a translational cancer imaging research program. His current joining Tayyaba Hasan’s laboratory in 2008 he has become immersed in research interests include fighting treatment-resistant ovarian cancer, tumor biology, animal models of cancer, and translational research. His spectroscopic and interferometric imaging technologies, and photodynamic current research aims to develop online microendoscopic molecular therapy. He was recently selected to join the Wellman faculty through a imaging for monitoring tumor cell signaling during treatment towards the competitive search and holds an appointment at Harvard Medical School. rational design of combination treatments for pancreatic and ovarian cancer. nously or topically, followed by illumination using a light delivery system suitable for the anatomical site being treated followed by detailed discussions of specific applications of (Figure 1B). The time delay, often referred to as the imaging in PDT. Each section starts with an overview of drug-light interval, between PS administration and the start the specific topic and, where appropriate, ends with a of illumination with currently used PSs varies from 5 min summary and future directions. The review closes with the to 24 h or more depending on the specific PS and the target authors’ perspective of the areas of future emphasis and disease. Strictly speaking, this should be referred to as the promise. The basic premise of this review is that a combina- PS-light interval, as at the concentrations typically used the tion of imaging and PDT will provide improved research PS is not a drug, but the drug-light interval terminology and therapeutic strategies. seems to be used fairly frequently. Typically, the useful range PDT is a photochemistry-based approach that uses a light- of wavelengths for therapeutic activation of the PS is activatable chemical, termed a photosensitizer (PS), and light 600-800 nm to avoid interference by endogenous chro- of an appropriate wavelength to impart cytotoxicity via the mophores within the body and yet maintain the energetics generation of reactive molecular species (Figure 1A). In necessary for the generation of cytotoxic species (as dis- 1 clinical settings, the PS is typically administered intrave- cussed below) such as singlet oxygen ( O2). However, it is Imaging and Photodynamic Therapy Chemical Reviews, 2010, Vol. 110, No. 5 2797 Kimberley S. Samkoe is a postdoctoral fellow at the Thayer School of Brian W. Pogue, Ph.D., received his B.Sc. Honors degree and M.Sc. Engineering at Dartmouth College (Hanover, NH, U.S.A.). She obtained degree from York University, Canada, in 1989 and 1991, respectively. her B.Sc. (Hons) in Biochemistry from the University of Regina (Regina, He completed his Ph.D. in Physics from McMaster University in 1995 SK, Canada) in 2001 and her Ph.D. from the University of Calgary and a postdoctoral research at the Wellman Center for Photomedicine
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