Abstract

Molecular imaging is a field widely used in the diagnosis and treatment of cancer. We offer here a modular method for the synthesis of targeted molecular imaging agents (TMIAs), which will improve the accuracy of current molecular imaging methods, as well as allow for earlier detection of tumors. The use of TMIAs in molecular imaging yields increased signal at cancerous cells and reduced signal from healthy cells. Our modular approach is useful as a facile method for the synthesis of dual-modal TMIAs for PET-MRI, which combine the sensitive detection of functional activity from PET with the high-resolution structural information obtained by MRI. Here, we present the synthesis of both a TMIA for the MRI of prostate cancer, followed by the synthesis of a dual-modal TMIA for use in simultaneous MRI-PET. By our method, a lysine backbone is utilized for the synthesis of imaging modules, by means of coupling the DOTA cyclene to the side chain of the lysine. A metal such as Gd3+ for use as an MRI contrast agent is chelated by DOTA. The imaging module is then coupled to a targeting moiety, such as c(RGDyK), through a carbon linker such as DSS or SMCC, to yield a novel TMIA. This same method is applied to the synthesis of dual-modal TMIAs featuring imaging modules for use in both MRI and PET. In the case of PET, where a radioactive isotope is required, we utilize a stable lanthanide placeholder that can be replaced by a useful metal isotope, such as 64Cu, at the end of the synthesis. Through the course of this research, our modular approach to the synthesis of TMIAs has proven to be an effective method of synthesis, and intermediate steps have been optimized. Additionally, methods of measuring the relaxivity of MRI contrast agents have been applied to our novel compounds for comparison with commercial agents available in clinical labs, hospitals, and imaging centers today.

Publication Date

6-2019

Document Type

Thesis

Student Type

Graduate

Degree Name

Chemistry (MS)

Department, Program, or Center

School of Chemistry and Materials Science (COS)

Advisor

Hans Schmitthenner

Advisor/Committee Member

Scott Williams

Advisor/Committee Member

Joseph Hornak

Campus

RIT – Main Campus

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