The goal of this proposal is to allow the PI to become a leading member of a multidisciplinary biomedical team that develops photonics-based systems to diagnose and treat cancer, with a focus on clinical translation of emerging nanoparticle technologies. This proposal outlines a mentored-training program, which places the candidate within a cluster of NIH funded researchers, including an NIH Center of Cancer Nanotechnology Excellence at Dartmouth (DCCNE). The plan involves 4 complementary areas of focus: 1) building a firmer base of cancer biology knowledge;2) developing superior theoretical and experimental expertise in standard biomedical imaging systems;3) experience leading a pre-clinical investigating of an experimental nanoparticle anti-cancer treatment;and 4) experience in translation of a developed approach/device into an ongoing clinical trial. To achieve these goals the candidate will use the funding to dedicate time to participate in graduate cancer, imaging, and translational medicine courses at the College and Medical School, and to attend cancer workshops, training seminars and grand rounds lectures. This knowledge base will be applied within an ongoing program project conducted by DCCNE, which is carrying out human trials in magnetic-nanoparticle (mNP)-mediated alternating magnetic field (AMF) therapy as a targeted treatment for solid malignant tumors. The DCCNE teams lack a practical method to quantitatively determine the distribution of mNPs within a selected tissue of interest following administration, a critical limitation given the large variance in structure and vascularity between tumor types. The research project component of this proposal will utilize a novel optical system design to probe absorption and fluorescence to quantitatively estimate mNP distribution in vivo, returning mNP concentrations independent of distortions from background optical properties. The 4 research aims of this project investigate the concept that mNP-AMF therapy requires accurate dosimetry of mNP uptake in order to quantitatively interpret, and optimally reduce, the individual variation expected between subjects.
Aim (1) is to design a novel optical device that will be validated for quantitative optical measurements of mNP in tissues in vivo.
Aim (2) is to characterize the mNP uptake and distribution of mNPs in both tumor and surrounding normal tissues in vivo.
Aim (3) will use quantitative dosimetry to monitor and optimize therapeutic dose delivered during preclinical mNP-AMF treatments. The prognostic value of mNP uptake measurements will be assessed by comparison with tumor growth delay. These data will be used to test the hypothesis that tumor- specific mNP-AMF dosimetry can optimize the delivered dose by reducing variability in treatment outcome.
Aim (4) is to integrate these optical techniques to obtain observational measurements into an ongoing pilot clinical study of mNP-AMF for treatment of breast cancer. Data acquired in this trial will be retrospectively analyzed to determine correlation between tumor response and measured mNP concentrations at the time of treatment. This proposal includes a multi-disciplinary group of mentors that possess expertise in cancer biology, surgery, radiation oncology, veterinary medicine, biomedical optics and imaging, clinical practice, and clinical translation and have ample expertise in NIH funding.
This proposal will provide the mentored-training required for the candidate to transition from a quantitative background in biomedical optics to become a biomedical researcher in the areas of cancer diagnostics and therapies. The research project portion of the proposal will use simple optical measurements of tissue parameters to optimize an experimental nanoparticle mediated anti-cancer treatment. The written critiques and criteria scores of individual reviewers are provided in essentially unedited form in the Critique section below. Please note that these critiques and criteria scores were prepared prior to the meeting and may not have been revised subsequent to any discussions at the review meeting. The Resume and Summary of Discussion section above summarizes the final opinions of the committee.
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