Date of Degree

9-2018

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Brian M. Zeglis

Committee Members

Jason S. Lewis

Lynn C. Francesconi

Rein V. Ulijn

Kevin H. Gardner

Subject Categories

Radiochemistry

Keywords

Pretargeting, Radiochemistry, peptide amphiphile

Abstract

The role of antibody-based imaging of cancer by positron emission tomography (PET) has expanded significantly in recent years and is poised to radically alter the way that cancer is diagnosed and treated. However, one hurdle that remains is the potentially harmful radiation dose that comes from these imaging agents, as the long circulation time of antibodies (days to weeks) necessitates the use of radionuclides with comparable physical half-lives (i.e. 89Zr, 124I, etc.). One particularly promising solution is the use of the inverse electron demand Diels-Alder (IEDDA) reaction between a 1,2,4,5-tetrazine (Tz) and a trans-cyclooctene (TCO) for pretargeting. By separately injecting antibody and radioligand and allowing the two to “click” in vivo, overall dose to the patient can be reduced nearly 45-fold. The first half of the dissertation to follow seeks to optimize both antibody and radioligand, while setting the stage for eventual clinical translation. The second half explores the emergence of enzyme-responsive nanomaterials in an attempt to develop a PET imaging agent for MMP-9 activity.

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