Dartmouth researchers have developed a fluorescence imaging technique that can more accurately identify receptors for targeted cancer therapies without a tissue biopsy. They report on their findings in a recently published article in Cancer Research.1
“Protein overexpression is a hallmark of certain cancers and is used in clinical oncology to personalize treatment through tumor detection, molecular therapies, and therapeutic monitoring,” said lead author Kimberley S. Samkoe, PhD, Assistant Professor of Surgery at the Geisel School of Medicine and Adjunct Assistant Professor at Thayer School of Engineering. “Protein expression is currently measured through a total protein analysis of tumor tissue. This new technique allows us to accurately determine the amount of protein receptors available for binding a drug without invasive biopsy.”
Study Details
The researchers developed a dual-tracer in vivo receptor concentration imaging technique that involves the simultaneous injection of both a targeted and a nontargeted imaging agent. They then studied the protein expression of five tumors, comparing the receptor concentration imaging data to that determined by clinical immunohistochemistry, either scored by a pathologist (as performed in the clinic) or analyzed independently by a computer.
They found that the protein expression determined by receptor concentration imaging strongly correlated to that determined by tissue analysis. They also found that commonly used techniques of measuring protein expression, such as Western blots or flow cytometry, did not correlate to the receptor concentration imaging values, and in fact overpredicted the number of receptors available for therapeutic or diagnostic targeting.
Potential Impact on Outcomes
“Accurately determining the population of protein receptors in a tumor available for targeting by molecular therapies or diagnostic imaging agents can greatly impact oncology patient outcomes,” said Dr. Samkoe.
“Our in vivo receptor concentration imaging technique is a novel approach for fluorescence imaging that can potentially impact clinical assessment of tumor status and malignant tissue classification,” she added.
Dr. Samkoe noted that this study looks at the average receptor expression within the tumor. The next step will be to look at tumors on a microscopic level in order to correlate receptor expression to distinct physiological features such as cellular viability, cellular type, vascularity, and overall tumor architecture.
The study was a collaboration between Geisel School of Medicine at Dartmouth College, the Thayer School of Engineering, members of the Norris Cotton Cancer Center, and the Wellman Center for Photomedicine at Massachusetts General Hospital. ■
Disclosure: The study was supported by NIH grants R01CA156177, U54CA151662 and P01CA84203. For full disclosures of the study authors, visit cancerres.aacrjournals.org.
Reference
1. Samkoe KS, Tichauer KM, Gunn JR, et al: Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach. Cancer Res. October 24, 2014 (early release online).
