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Quantitative PET/CT Imaging Based Biodistribution Validated in a Porcine Model using a Targeted Peptide Radiotracer, AMBA

Layman, Ricky R, Jr

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2013, Doctor of Philosophy, Ohio State University, Biophysics.
In 2010, about 562,340 Americans died of cancer, more than 1,500 people a day making it the second most common cause of death in the US after heart disease.(1) Traditional cancer treatment includes surgery, chemotherapy, biological agents, radiation treatment and endocrine therapy in which regimens are applied based on diagnostic tests that have limitations in predicting response. As a result, there is a critical need to improve the detection and characterization of disease with biomarker capable, quantitative imaging readouts. This project will specifically focus on this topic in oncology by advancing quantitative imaging through improved detection, staging and response assessment along with the development of targeted imaging probes that can identify specific biomarkers or pathways to enable disease specific detection and characterization—personalized medicine. The advancement of diagnostic imaging has improved significantly since the early 1980’s primarily due to the clinical introduction and availability of advanced cross-sectional modalities such as magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET) that were able to improve detection and visualization of disease. Imaging capabilities were advanced further in the early 2000’s when hybrid imaging systems such as PET and CT enabled the correlation of disease metabolic activity detected with PET to be co-registered with anatomic and morphologic findings from CT. Success similar to PET/CT can be achieved with the development and advancement of additional hybrid systems (i.e. SPECT/PET/MR/CT/US/UV) where the strengths of one system can be complemented by the strengths of another for improved quantification and characterization of disease. The evaluation of biological response requires targeted imaging probes that are biomarker capable and enable quantitative readouts. Furthermore, targeted imaging probes provide the opportunity to improve therapeutic response rates by identifying patients prior to treatment that are more likely to respond. The targeted imaging probe can be chemically modified to a therapeutic agent with the attachment of the appropriate radioisotope (i.e. beta emitter) that can kill cancer cells enabling the treatment of disease, including systemic disease. Theranostics is the application of drugs that can act as both a diagnostic imaging and therapeutic agent which provides unique opportunities since the same targets or pathways are evaluated for diagnostics and therapy. Additional opportunities and applications in quantitative imaging can also be achieved with the utilization of theranostics for improved staging and response assessment. The development of quantitative hybrid PET/CT requires optimization of post-processing, reconstruction, attenuation correction and co-registration enabling image based biodistribution for improved patient selection, staging, response assessment, and individualized patient specific therapeutic regimens using molecular imaging agents. Overall Aim: The development and application of a quantitative algorithm for PET/CT imaging will minimize imaging bias and improve quality for an imaging based biodistribution to humans. Aim 1: PET/CT image degradation from partial volume effects will be reduced with the application of a point spread function to the reconstructed PET images for improved quantification. Aim 2: Additional improvements in PET/CT image quality and quantification will be obtained by characterizing and correcting for scatter and attenuation effects. Aim 3: Corrections for imaging bias related to partial volume, scatter and attenuation effects will lead to a new quantitative algorithm for validation in a porcine model with radiotracer accumulation verified in select, resected organs and quantitative accuracy confirmed with an accurate radiation counting system.
Michael V. Knopp, MD, PhD (Advisor)
Michael F. Tweedle, PhD (Committee Member)
Edward T. Martin, MD (Committee Member)
Nathan Hall, MD, PhD (Committee Member)
Honscheid Klaus, PhD (Committee Member)
107 p.

Recommended Citations

Citations

  • Layman, Jr, R. R. (2013). Quantitative PET/CT Imaging Based Biodistribution Validated in a Porcine Model using a Targeted Peptide Radiotracer, AMBA [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374113662

    APA Style (7th edition)

  • Layman, Jr, Ricky. Quantitative PET/CT Imaging Based Biodistribution Validated in a Porcine Model using a Targeted Peptide Radiotracer, AMBA. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1374113662.

    MLA Style (8th edition)

  • Layman, Jr, Ricky. "Quantitative PET/CT Imaging Based Biodistribution Validated in a Porcine Model using a Targeted Peptide Radiotracer, AMBA." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374113662

    Chicago Manual of Style (17th edition)