This project advances the use of two novel technologies to image tissue in experimental cancer models and in patients, and will test hypothesis that these can be used to image tissue biophysical parameters, photosensitizer concentration and blood flow in tumors. The central theme in this project is that optical spectroscopy can be used in vivo to accurately measure bulk tissue values, but must be used in a way, which is image-guided. Image-guided spectroscopy utilizes transmission or remission measurements for their superior signal to noise in measuring molecular concentration in vivo, yet also allows integration of the measurement into existing medical imaging technologies, such as magnetic resonance imaging (MRI), high frequency ultrasound (HFUS), and optical coherence tomography (OCT).
Aim 1 utilizes a commercial prototype system for combined MRI-NIR tomography of experimental rodent models, to study the biophysical changes in hemoglobin, oxygen saturation, water and sub-cellular granularity which can be assessed by NIR tomography. The changes in response to chemotherapy and receptor signaling can be measured by longitudinal imaging studies using this new imaging system. The pancreas cancer model will also be used to validate the imaging, by systematic and quantitative comparison to ex vivo measurements.
In Aim 2, the ability to combine fluorescence optical tomography with structural imaging systems such as OCT and HFUS will be tested, as a way to quantify the photosensitizer concentrations in skin. These unique hybrid systems will be validated in phantoms and tissue cultures, and then used to study skin cancer tumors in vivo. Finally Aim 3 will advance the concept of using photosensitizer imaging as a way to individualize dosimetry treatment planning, using the systems described above. The uptake rate in the tissue can be quantified using image-guided absorbance imaging. This work will also involve modeling of the parenchyma versus vascular partitioning of the drug in a pancreas tumor model, to aid in the related studies of clinical pancreas cancer PDT. The project will translate key developments to Core C, for eventual distribution to other projects, and will use software tools developed in the core. The project uses microscopy analysis and knowledge from Core B to analyze the histology sections, to validate the in vivo imaging with ex vivo quantitative pathology. The project uses common tumor models from the other projects and Core B, and also leverages considerable imaging resources from ongoing work in tools for optical imaging, Potential benefit to public health: this project provides new tools for basic PDT dosimetry and translated into clinical PDT dosimetry thus enhancing treatment outcomes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA084203-09
Application #
8374937
Study Section
Special Emphasis Panel (ZCA1-GRB-P)
Project Start
Project End
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
9
Fiscal Year
2012
Total Cost
$208,902
Indirect Cost
$40,584
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce et al. (2016) Photodynamic Therapy Synergizes with Irinotecan to Overcome Compensatory Mechanisms and Improve Treatment Outcomes in Pancreatic Cancer. Cancer Res 76:1066-77
Tangutoori, Shifalika; Spring, Bryan Q; Mai, Zhiming et al. (2016) Simultaneous delivery of cytotoxic and biologic therapeutics using nanophotoactivatable liposomes enhances treatment efficacy in a mouse model of pancreatic cancer. Nanomedicine 12:223-34
Obaid, Girgis; Broekgaarden, Mans; Bulin, Anne-Laure et al. (2016) Photonanomedicine: a convergence of photodynamic therapy and nanotechnology. Nanoscale 8:12471-503
Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S et al. (2016) Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention. Med Phys 43:3143
Pogue, Brian W; Elliott, Jonathan T; Kanick, Stephen C et al. (2016) Revisiting photodynamic therapy dosimetry: reductionist & surrogate approaches to facilitate clinical success. Phys Med Biol 61:R57-89
Huggett, Matthew T; Tudzarova, Slavica; Proctor, Ian et al. (2016) Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint. Oncotarget 7:18495-507
Spring, Bryan Q; Bryan Sears, R; Zheng, Lei Zak et al. (2016) A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways. Nat Nanotechnol 11:378-87
de Souza, Ana Luiza Ribeiro; Marra, Kayla; Gunn, Jason et al. (2016) Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer. Br J Cancer 115:805-13
Mohammad, Goran Hamid; Olde Damink, S W M; Malago, Massimo et al. (2016) Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome. PLoS One 11:e0151635
Mallidi, Srivalleesha; Mai, Zhiming; Rizvi, Imran et al. (2015) In vivo evaluation of battery-operated light-emitting diode-based photodynamic therapy efficacy using tumor volume and biomarker expression as endpoints. J Biomed Opt 20:048003

Showing the most recent 10 out of 150 publications