Keith M. Stantz, Ph.D. Assistant Professor of Health Sciences Adjunct Professor of Radiology, Indiana University School of Medicine Phone: (765) 496-1874 E-mail: kstantz@purdue.edu Full directory listing

Education

Research: Molecular and Physiological Imaging of Hypoxia and Cancer

An evolving paradigm to improve cancer therapy is to combine new generations of drugs with traditional cytotoxic therapies in the hope of improving patient outcome and quality of life.

Purpose: The purpose of my research is to develop instrumentation and imaging techniques which will be used to explore the tumor's microenvironment and biomolecular mechanisms by which anti-angiogenic therapy (AAT) can enhance current cancer therapies.

Background: Tumor angiogenesis is an unregulated biomolecular process resulting in the formation of a chaotic and dysfunction vasculature that varies both spatially and temporally. The haphazard delivery of (or barriers to) oxygen and drugs form pockets and/or regions of hypoxia and uneven distribution of chemotherapy agents. This property of tumors called intra-tumor heterogeneity is a major factor contributing to the ineffectiveness of cancer therapies. AAT has the potential to normalize tumor vasculature, e.g., ameliorate intra-tumor heterogeneity. Normalization of tumor vasculature has the potential to enhance cancer therapy by (1) delivering oxygen and drugs to a higher fraction of cancer cells in the tumor and (2) down-regulating stress-related chemoresistant factors (HIF1α, NF-κB) and pro-survival proteins (Bcl-2, Bcl-X_L). Key to the staging of cancer therapy is the ability to monitor in vivo the response of the tumor phenotype to AAT using novel imaging technologies and techniques.

Interests

Physiological Imaging using DCE-CT

• Quantify intra-tumor physiology (perfusion, PS, fp, fis)
• Influence of tumor angiogenesis in tumor progression, and barriers to drug delivery
• Influence of VEGF/VEGFR2 paracrine interaction on tumor intra-heterogeneity, and its longitudinal response to flk1/KDR receptor blockade

Molecular Imaging using Photoacoustic CT-spectroscopy

• Quantify intra-tumor hemoglobin concentrations and oxygen saturation levels (SaO₂)
• In vivo imaging of oxidative stress by developing mathematical models that will fuse tumor physiology and hemoglobin state.
• Quantify follicle stimulating hormone receptor (FSHR) expression in ovarian tumors.
• In vivo imaging of drug delivery vehicles

Biomolecular

• Correlation to chemoresistant factors HIF1α and NF-κB, and potential down-stream anti-apoptotic factors (Bcl-2 family), to hypoxia

Representative Publications

Stantz KM, Liang Y, Hutchins, Gary; "Kinematic Modeling and Its Implication in Longitudinal Chemotherapy Study of Tumor Physiology: Ovarian Xenograft Mouse Model and Contrast-Enhanced Dynamic CT," Proc. SPIE Medical Imaging 5369:769-779, 2004.

Stantz KM, Liang Y, Li X, Kao C, Steinmetz R, Imaging the Progression of Intra-tumor Heterogeneity in Prostate and Ovarian Xenografts using Dynamic Contrast-Enhanced CT, Proc. IEEE EMBC, 2005.

Stantz KM, Liu B, Cao Minsong, Reinecke D, Dzemidzic M, Liang Y, Kruger R. "Evaluating Dynamic Contrast-Enhanced and Photoacoustic CT to Assess Intra-Tumor Heterogeneity in Xenograft Mouse Models", Proc. SPIE Medical Imaging 6143:489-500, 2006.

Stantz KM, Liu B, Cao M, Reinecke D, Miller K, Kruger R, "Photoacoustic spectroscopic imaging of intra-tumor heterogeneity and molecular identification", Proc. SPIE BIOS 6086:36-47, 2006.

Stantz KM, Cao M, Liang Y, Miller KD, "Evaluating the Therapeutic Response of PS-341 in Xenograft SKOV3x Ovarian Mouse Model by Dynamic Contrast-Enhanced CT", Molecular Imaging and Biology 8(2):73-74, 2006.

Cao M, Liang Y, Miller KD, Stantz KM, "Quantification of Intra-Tumor Physiological Heterogeneity and Therapeutic Response in Xenograft MCF-7 Breast Cancer Model by Dynamic Contrast Enhanced Computed Tomography", Molecular Imaging and Biology 8(2):71, 2006.

Liu B, Reinecke D, Kruger RA, Stantz KM, "Phantom and in-vivo measurements of hemoglobin concentration and oxygen saturation using PCT-S small animal scanner", Proc. SPIE BIOS 6437:, 2007.

Stantz KM, Liu B, Kruger RA, "Using Monte Carlo simulations to understand the influence of photon propagation on photoacoustic spectroscopic imaging", Proc. SPIE BIOS 6437:, 2007