Gary D. Hutchins - US grants

bioimaging /biomedical imaging; diagnosis quality /standard; disease /disorder model; heart imaging /visualization /scanning; imaging /visualization /scanning; positron emission tomography

The goal of the Indiana-ICMIC planning grant is to foster collaboration between scientist involved in the development and application of in-vivo and in-vitro imaging methodologies with investigators involved in the extensive basic science and clinical cancer research programs of the Indiana University Cancer Center (IUCC). This pre-ICMIC planning grant program provides a unique opportunity to facilitate the integration of many currently disparate cancer research and imaging programs within our institution. While the overall goal of this program is to develop and apply non-invasive in-vivo imaging methods that are suitable for use in cancer patients, we feel that current state-of-the-art in-vivo imaging techniques cannot provide all of the important information available through imaging technologies at the present time. Therefore, we have chosen an approach in which we will utilize both in-vivo and in-vitro imaging methods to aid in the study and development of cancer therapies. Our overall hypothesis is that in-vivo imaging applications that elucidate unique physiologic mechanisms in neoplastic disease will serve as important surrogate markers for the presence of cancer and its response to therapy. The research specific aims of this program will be: 1) Identification and development of tracers and/or contrast agents to monitor gene expression and cellular physiology, 2) Development of novel in vitro and in vivo imaging methodologies for the study of cellular and molecular processes, and 3) Application of in vitro and in vivo imaging methods to monitor tumor cellular physiology and gene expression. The primary focus of this planning grant will be the development of 5-6 cancer imaging research programs that will form the basis of a comprehensive ICMIC application within the next 2-3 years.

Abstract Current imaging-based techniques for quantitative assessment of tissue perfusion require complex data acquisition and analysis strategies; typically require ancillary blood sampling for measurement of input functions; are limited to a single organ or tissue region; and because of their complexity are not well suited as a biomarker for cancer clinical trials or patient management. We hypothesize that the 62Cu-labeled copper(II) bis(thiosemicarbazone) complexes, Cu-ETS and Cu-ETSM, will provide a platform for quantitative estimation of tissue perfusion throughout whole-body images utilizing methods that are rapid, and computationally suitable, for widespread routine clinical application. The objective of this academic-industrial partnership proposal is to translate very promising initial results into a fully validated whole-body quantitative perfusion imaging method for use as a biomarker in cancer clinical trials and precision medicine treatment strategies. This partnership will bring together three key teams of investigators to: i. fully develop and validate the 62Cu quantitative perfusion method (Indiana University); ii. refine the 62Zn/62Cu generator production technology to enable wide-spread generator distribution (Zevacor Molecular, Inc.); and iii. to establish a software processing platform to facilitate harmonization of data analysis across diverse imaging centers (MIM Software, Inc. and Indiana University). The significance of this research includes the abilities to: (1) quantitatively assess the vascular effects of therapeutic agents on tumors throughout the body; (2) assess non-target side-effects in tissues throughout the whole body; (3) establish disease phenotype in both primary and metastatic lesions (and patient prognosis) by combining whole-body metabolism and perfusion measurements; (4) monitor the transition of tumors from a drug-responsive to a drug-resistant phenotype (and/or assess durability of response); (5) assess the extent of comorbidities that manifest with perfusion abnormalities (e.g., cardiovascular, cerebrovascular, renal, and peripheral vascular diseases, diabetes, thyroid function); (6) widely distribute 62Zn/62Cu generators to meet clinical trial and patient care demands; and (7) harmonize implementation of this method across diverse imaging environments via standardized quantitative data and image analysis tools. The key innovation of this research will be advancement of a quantitative whole-body perfusion imaging method from the research laboratory into a complete set of validated tools that enable robust and standardized application in clinical trials and patient care throughout the imaging community.