AbstractCurrent imaging-based techniques for quantitative assessment of tissue perfusion require complex dataacquisition and analysis strategies; typically require ancillary blood sampling for measurement of inputfunctions; are limited to a single organ or tissue region; and because of their complexity are not well suited as abiomarker 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 estimationof tissue perfusion throughout whole-body images utilizing methods that are rapid, and computationallysuitable, for widespread routine clinical application. The objective of this academic-industrial partnershipproposal is to translate very promising initial results into a fully validated whole-body quantitative perfusionimaging 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 62Cuquantitative perfusion method (Indiana University); ii. refine the 62Zn/62Cu generator production technology toenable wide-spread generator distribution (Zevacor Molecular, Inc.); and iii. to establish a software processingplatform to facilitate harmonization of data analysis across diverse imaging centers (MIM Software, Inc. andIndiana University). The significance of this research includes the abilities to: (1) quantitatively assess thevascular effects of therapeutic agents on tumors throughout the body; (2) assess non-target side-effects intissues 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 thetransition of tumors from a drug-responsive to a drug-resistant phenotype (and/or assess durability ofresponse); (5) assess the extent of comorbidities that manifest with perfusion abnormalities (e.g.,cardiovascular, cerebrovascular, renal, and peripheral vascular diseases, diabetes, thyroid function); (6) widelydistribute 62Zn/62Cu generators to meet clinical trial and patient care demands; and (7) harmonizeimplementation of this method across diverse imaging environments via standardized quantitative data andimage analysis tools. The key innovation of this research will be advancement of a quantitative whole-bodyperfusion imaging method from the research laboratory into a complete set of validated tools that enable robustand standardized application in clinical trials and patient care throughout the imaging community.
|Effective start/end date||7/1/16 → 6/30/21|
- National Institutes of Health: $591,408.00