Abstract P5-01-10: In vitro and in vivo imaging of Her2 with cyclic peptides derived from directed evolution
Abstract The implementation of personalized medicine for Her2-positive breast cancer treatment (Trastuzumab and Pertuzumab) has made a dramatic effect on overall patient outcome. Unfortunately, there are currently no FDA-approved imaging agents to monitor Her2-positive breast cancer leaving physicia...
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Published in | Cancer research (Chicago, Ill.) Vol. 75; no. 9_Supplement; pp. P5 - P5-01-10 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.05.2015
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Online Access | Get full text |
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Summary: | Abstract
The implementation of personalized medicine for Her2-positive breast cancer treatment (Trastuzumab and Pertuzumab) has made a dramatic effect on overall patient outcome. Unfortunately, there are currently no FDA-approved imaging agents to monitor Her2-positive breast cancer leaving physicians to rely on invasive biopsies and anatomical imaging to monitor treatment with Her2-targeted therapeutics. There is also increasing evidence that women initially diagnosed with Her2-negative breast can present with Her2-positive disease upon recurrence. Noninvasive, whole-body visualization of Her2 would identify Her2-recurrent disease and serve as a powerful tool to monitor the effectiveness of new and emerging Her2-targeted therapeutics (e.g. TDM-1). While many Her2-antibody based imaging agents have been used in preclinical applications, their long circulating half-lives, high liver uptake, and poor synthetic accessibility pose a challenges for clinical translation. Here we describe the use of highly stable cyclic peptides derived from biological display as imaging agents for Her2-positive breast cancer. These peptides have antibody-like high affinity (<10 nM) for Her2-positive tumors and their size (<2 kDa) allows for higher rates of clearance, lower background signal, and consequently higher image sensitivity. Anti-Her2 peptides were pre-optimized for affinity, protease resistance and bio-stability prior to labeling with the Cy7.5 near-infrared dye. Her2-specificity was determined by in vitro assays with Her2-postive (BT474 and SKOV3), HER2-normal (MCF7) and Her2-negative (MDA-MB-231) cell lines. Sequences that showed superior affinity and selectivity were used to acquire fluorescent images of ectopic and orthotopic murine models of Her2-positive breast cancer. Our preliminary imaging data suggests that this scaffold has excellent translational potential for targeted molecular imaging of Her2-postive breast cancer.
Citation Format: Lindsay E Kelderhouse, Amanda Hardy, Yong Pan, Patrea Rhea, Argentina Ornelas, Seth Gammon, Peiying Yang, Stephen Fiacco, Steven W Millward. In vitro and in vivo imaging of Her2 with cyclic peptides derived from directed evolution [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-10. |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.SABCS14-P5-01-10 |