SBIR-STTR Award

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 CLR is proposed as a neoadjuvant therapy option for TNBC patients In the first aim of this proposal I will conjugated to a tumor targeting moiety CLR Subsequently the physico chemical properties of I CLR will be characterized and the chemical reactions to maximize chemical yield and minimize the amount of chemical impurities will be optimized I CLR will be synthesized reliably with a radiochemical yield rt a radiochemical purity final product rt and chemical purity final product rt In the second aim I CLR 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 CLR in an appropriate murine model of TNBC will be conducted It is hypothesize that neoadjuvant I CLR leads to reduced tumor metastasis and improved survival in clinically relevant mouse models of TNBC

___(NOTE: Note: no official Abstract exists of this Phase II projects. Abstract is modified by idi from relevant Phase I data. The specific Phase II work statement and objectives may differ)___ 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 CLR is proposed as a neoadjuvant therapy option for TNBC patients In the first aim of this proposal I will conjugated to a tumor targeting moiety CLR Subsequently the physico chemical properties of I CLR will be characterized and the chemical reactions to maximize chemical yield and minimize the amount of chemical impurities will be optimized I CLR will be synthesized reliably with a radiochemical yield rt a radiochemical purity final product rt and chemical purity final product rt In the second aim I CLR 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 CLR in an appropriate murine model of TNBC will be conducted It is hypothesize that neoadjuvant I CLR leads to reduced tumor metastasis and improved survival in clinically relevant mouse models of TNBC