Access Type

Open Access Dissertation

Date of Award

January 2019

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Cancer Biology

First Advisor

Nerissa T. Viola-Villegas

Abstract

With a broad spectrum of therapies available for treating breast cancer, the need for personalized medicine tailoring the cure according to phenotype is evident. Such an approach may be fully realized with the development of quantitative imaging technologies for disease detection, staging and diagnosis, without increasing patient burden. Immuno-positron emission tomography (PET) combines the targeted specificity of antibodies with the sensitivity of PET for whole body imaging by targeting molecular features amplified in lesions. ImmunoPET probes targeting different antigens and their utility to measure response to treatment were explored. 89Zr-trastuzumab was employed as a surrogate readout of Src inhibition after dasatinib treatment in HER2+ breast cancer. 89Zr-cetuximab was also employed to measure cell-surface EGFR expression following dasatinib treatment in triple negative breast cancer. Tumor infiltrating T-cells were measured using 89Zr-anti-CD3 and 89Zr-anti-IFN after vaccination in a murine model of breast cancer. All studies utilized in vitro uptake assays, autoradiography, IHC, and western blots to validate tracer specificity. PET scans were analyzed after treatment to determine changes in tracer retention. In each study PET was able to detect tumor uptake changes which occurred early (within 1 week) or treatment. Through these projects we provide clinically relevant imaging strategies to better predict treatment outcomes and aid clinicians in cancer management.

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