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.
This academic-industrial partnership will develop and validate the first quantitative whole-body tissue perfusion method designed specifically for widespread application in clinical research and patient care. Perfusion is responsible for the delivery and exchange of oxygen, nutrients, and drugs to tissues, and therefore, plays an essential role in both tissue physiology (normal tissues and cancer) and response to therapy. This diagnostic tool is expected to enhance our knowledge about cancer and its response to therapy, characterize the effects of new cancer drugs in clinical trials, and help guide individualized patient treatment protocols.
| Territo, Paul R; Riley, Amanda A; McCarthy, Brian P et al. (2016) Measurement of cardiovascular function using a novel view-sharing PET reconstruction method and tracer kinetic analysis. EJNMMI Phys 3:24 |
