Research Project
9324025
Poor prognosis of triple negative breast cancer (TNBC) is attributable to the absence of efficacious, molecularly-targeted, neoadjuvant therapies. Micrometastases contribute to poor prognosis by increasing recurrence rate. Consequently, an effective treatment option that is capable of targeting and sterilizing micrometastatic disease in patients with TNBC is warranted. I-125-CLR1404 is proposed as a neoadjuvant therapy option for TNBC patients. In the first aim of this proposal, I-125 will conjugated to a tumor-targeting moiety, CLR1404. Subsequently, the physico-chemical properties of I-125-CLR1404 will be characterized and the chemical reactions to maximize chemical yield and minimize the amount of chemical impurities will be optimized. I-125-CLR1404 will be synthesized reliably with a radiochemical yield > 60%, a radiochemical purity (final product) > 95%, and chemical purity (final product) >90.0%. In the second aim, I-125-CLR1404 will be characterized biologically in murine TNBC models. This will include the assessment of pharmacokinetics, radiation dosimetry, and the investigation of normal tissue toxicities. Hematological toxicity will most likely be dose-limiting. In the final aim, efficacy studies of I-125-CLR1404 in an appropriate murine model of TNBC will be conducted. It is hypothesize that neoadjuvant I-125-CLR1404 leads to reduced tumor metastasis and improved survival in clinically relevant mouse models of TNBC.
