This translational research project will develop quantitative imaging bionnarkers for assessing therapeutic response in Sarcoma using advanced quantitative imaging approaches in PET and MRl.
In Specific Aim #1, dynamic contrast enhanced (DCE) and diffusion weighted (DW) MRl will be evaluated in a multi-center clinical trial of patients with soft tissue sarcoma ofthe extremities receiving neoadjuvant chemotherapy prior to surgical resection. DCE- and DW-MRI imaging will be performed prior to and at the conclusion of chemotherapy to evaluate the correlation between treatment response assessed with MRl parameters (permeability, perfusion, and diffusion) and tumor histopathology obtained from surgical resection. Exploratory analysis will also be performed to compare imaging and pathologic response with clinical outcome.
In Specific Aim #2, two novel PET apoptosis probes (18F-ML-10 and 1241-Diannexin) will be evaluated and compared to existing PET probes for glucose metabolism (FDG) and cellular proliferation (FLT). Similar strategies will be employed in Specific Aim #3 to evaluate hwo novel PET probes for angiogenesis (i8F-FPP(RgD) and 892R-beYaci?Ufnat)). Preclinical microPET/CT imaQlno studiQS will bQ performed in several sarcoma mouse models using the comprehensive panel of PET probes in longitudinal treatment studies of various therapeutic agents. Correlations with tumor histopathology will be performed to validate the imaging assessments. In addition, DCE and DW MRl imaging will be performed in the same studies to compare the more specific PET assessments of metabolism, proliferation, angiogenesis, and apopotosis with the MRl perfusion and diffusion measurements that are more clinically available. This will further refine and validate the interpretation of MRl imaging response measured in Specific Aim #1 as well develop more specific PET imaging probes for future clinical trials. Together, the Specific Aims of this proposal will advance bi-directional translational research that enhances the knowledge of clinical MRl biomarkers for assessing early drug response in sarcoma therapy (bedside to bench) as well as develop novel PET imaging agents that are translatable to clinical trials and patient care (bench to bedside).
This project will develop new imaging approaches using MRl and PET to non-invasively measure various aspects of tumor biology and pathophysiology in response to conventional and experimental chemotherapies. This will enable a powerful set of tools to evaluate treatment efficacy and ultimately improve the development of new drugs and clinical management of sarcoma patients.
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