EC145 is a potent folate-targeted Vinca alkaloid conjugate that is currently being evaluated in a global phase 3 trial for the treatment of platinum-resistant ovarian cancer. By design, response to EC145 should be dependent on folate receptor (FR) expression. Therefore, characterizing the presence and functionality of the FR in real time is critical for the selection of patients for whom FR-targeted therapy may be beneficial. A promising method that's currently being co-developed with EC145 is to image patients prior to therapy using 99mTc-EC20, which is a small molecular weight folate-targeted companion imaging agent. Similar to EC145, 99mTc-EC20 binds to the FR with high affinity (Kd ∼ 3 nM) in a manner that is both saturable and independent of the cell type. 99mTc-EC20's binding specificity has been confirmed using validated preclinical models where it was found that i) binding of 99mTc-EC20 to cells or accumulation within solid tumors is dependent on FR expression (but independent of isoform), and ii) excess folic acid can competitively block 99mTc-EC20's cell/tissue binding. Furthermore, EC145 was also found to displace pre-bound 99mTc-EC20 from FR-positive tumors and kidneys in mice, strongly suggesting that EC145 and 99mTc-EC20 distribute similarly in vivo. Taken together, these findings indicate that the FR mediates tissue uptake of 99mTc-EC20. Since 99mTc-EC20 provides a non-invasive, real-time assessment of functionally active as well as anatomically-accessible FRs, this radiodiagnostic agent may predict what tissues will accumulate and potentially respond to folate-targeted drugs, such as EC145.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3622. doi:1538-7445.AM2012-3622