| This dissertation details the work focused on discovering and validating PET imaging agents which target calcifications in the breast and prostate. The presence of these calcifications is well known and has been utilized for various preventative screening methods for decades. However, the discovery that the composition of these calcifications is highly correlated with malignancy, is a relatively recent, yet extensively supported concept. We have dedicated the past four years to investigating methods to exploit this observation for the non-invasive diagnosis of breast and prostate cancers. We are therefore excited to report that, to the best of our knowledge, we are the first to develop a PET imaging agent, 64Cu-DOTA-alendronate, that can differentiate malignant vs. benign breast tumors based on the composition of calcifications. Furthermore, we have developed and characterized a novel animal model, the retired breeder aged female Sprague Dawley rat, that which is uniquely suited for evaluating breast imaging modalities and represents the first natural rodent model of mammary microcalcifications. Our work in discovering, validating, and safety testing 64Cu-DOTA-alendronate has produced excellent results, which are presented in the published paper "Diagnostic PET Imaging of Mammary Microcalcifications using 64Cu-DOTA-alendronate in a Rat Model of Breast Cancer." Based on these results we have initiated a human clinical trial at City of Hope which is anticipated to begin soon after the publication of this dissertation.;Our success with mammary microcalcifications has led us to investigate the prostate, another site where calcifications are present and indicative of cancer, as a potential target for calcification binding imaging agents. While less extensive as our work with alendronate, we present promising results with 64Cu-DOTA-BPEN as a calcification specific prostate imaging agent. The uptake of 64Cu-DOTA-BPEN in the prostate increases during hyperplasia and neoplasia and may present an imaging agent which can not only detect, but differentiate prostatic diseases. This dissertation serves as a timeline and written account of the extensive work that has gone into the discovery, development, improvement and evaluation of these imaging agents. |
