Quantitative imaging (QI) is positioned to play a central role in providing clinically relevant information about a tumor?s biology and its microenvironment to aid in the design of adaptive therapy trials. While standardization of QI methods have had a great impact in advancing clinical applications of QI to assess and predict response to therapy, preclinical imaging remains a critical component in the translational pipeline of validating advanced QI methods for applications in drug discovery and assessment of response to therapy. Thus, developing QI standards that transcend species and modalities is critical in advancing the application of QI. Standardization of preclinical QI has been limited primarily for two reasons: first, use of unrealistic animal models of cancer, such as established cell lines, to validate QI methods, and second, logistical and technical challenges inherent in preclinical imaging. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived cancer tissue xenograft (PDX). Leveraging the infrastructure available at Mallinckrodt Institute of Radiology (MIR), Human & Mouse Linked Evaluation of Tumors (HAMLET) Core of the Institute of Clinical and Translational Sciences (ICTS), and the Siteman Cancer Center, the WU-C2IR2 will harmonize, optimize, validate, and implement preclinical-clinical QI algorithms, bi-directionally, in a context of an active co-clinical TNBC trial. Interfacing with the HAMLET Core, the Resource will generate credentialed PDX mice matched to the patient?s tumor sub-type in addition to PDX mice generated from tumor biopsies/engraftments. QI algorithms will be optimized and validated in both settings and implemented in the co-clinical trial taking advantage of simultaneous PET/MR Biograph mMR to evaluate the efficacy of advanced multi-parametric PET and MR imaging methods to assess response to therapy in TNBC. To compliment QI efforts, multi-scale analytics of tissue samples will be collected including RNA Seq, pathology, Exome sequencing, among others to integrate with QI to facilitate prediction of response to therapy. All data will be uploaded to a dynamic and modular informatics resource available to the co-clinical community to test new algorithms, and mine for novel leads integrating imaging and multi-scale analytic data to predict therapeutic response in TNBC. Thus, the Resource will rigorously optimize the utility multi-parametric quantitative PET/MR imaging in assessing response to therapy in realistic animal models of cancer and patients and develop QI standards that transcend species and modalities which is critical in advancing the application of QI.
The proposal aims to establish a resource to optimize and validate quantitative imaging methods to assess or predict response to therapy using patient-derived tumors implanted in mice and the implementation of the quantitative methods in clinical imaging to facilitate assessment of therapy.
|Chan, Szeman Ruby; Salem, Kelley; Jeffery, Justin et al. (2018) Sex as a Biologic Variable in Preclinical Imaging Research: Initial Observations with 18F-FLT. J Nucl Med 59:833-838|