Michael Stanley Gee MD, PhD, Presenter: Nothing to Disclose

Rabi Upadhyay, Abstract Co-Author: Nothing to Disclose

Lee Josephson PhD, Abstract Co-Author: Nothing to Disclose

Ralph Weissleder MD, PhD, Abstract Co-Author: Nothing to Disclose

Umar Mahmood MD, Abstract Co-Author: Nothing to Disclose

To determine whether HER2/Neu inhibition, the direct therapeutic target of herceptin treatment, can be assessed noninvasively in human breast tumors by optical imaging with a near infrared dye-conjugated herceptin probe.

A probe for optical imaging was generated by conjugating herceptin with the near-infrared dye Cy5.5. Probe binding to HER2/Neu-low (MCF7) and HER2/Neu-high (BT474, SKBR3) human breast cancer lines was assessed by flow cytometry and fluorescence microscopy. Tumors were established by tumor cell implantation into the mammary glands of female nude mice. Noninvasive optical imaging of tumors before and after herceptin treatment was performed following intravenous administration of Cy5.5-herceptin.

Cy5.5-herceptin demonstrated greater than 10-fold increased binding to BT474 and SKBR3 cells compared with multiple HER2-low human cell lines (MCF7, BT20, Jurkat). Probe binding was competitively inhibited by addition of molar excess of cold (unlabeled) herceptin in a dose-dependent manner. Fluorescence microscopy confirmed probe localization to the cell surface in HER2-high lines. In vivo experiments demonstrated approximately 3-fold higher Cy5.5-herceptin binding to HER2-high tumors compared with size-matched HER2-low tumors 48 hours after intravenous probe administration. Treatment of HER2-high tumors with cold herceptin at doses sufficient to control tumor growth produced a decrease in tumor probe binding essentially to the level of HER2-low tumors.

Optical imaging with Cy5.5-herceptin can be used to assess herceptin inhibition of HER2/Neu noninvasively in human breast tumors. This approach has great potential as a noninvasive method to assess efficacy of cancer therapy with monoclonal antibodies and other molecular antagonists targeting tumor cell proteins.

Gee, M, Upadhyay, R, Josephson, L, Weissleder, R, Mahmood, U, Noninvasive Optical Imaging of HER2 Inhibition during Herceptin Treatment of Breast Cancer.  Radiological Society of North America 2005 Scientific Assembly and Annual Meeting, November 27 - December 2, 2005 ,Chicago IL. http://archive.rsna.org/2005/4410834.html