Yale scientists have pioneered a new form of positron emission tomography (PET). This new approach to imaging may allow cancer-care specialists to detect the epidermal growth factor receptor (EGFR), a target for cancer therapy that is expressed on the surface of tumor cells. This new type of PET scan will also monitor drugs that target the EGFR in tumors and could provide a new way to image their effectiveness in patients.
The most common form of PET scan is called fluorodeoxyglucose (FDG)-PET, in which a cancer patient is given a radioactive sugar that accumulates in the tumor, allowing doctors to view it. The Yale group is using PET technology in a way that hasn’t been done before. Their new technique uses a radiolabeled drug that specifically binds to the EGFR. The goal is to provide a method for doctors to see the tumor, watch the uptake of the drug, and monitor its effectiveness.
“That’s what we’re really excited about,” said Joseph Contessa, MD, PhD, Associate Professor of Therapeutic Radiology and Pharmacology whose laboratory studies the biology of EGFR. “We have not previously been able to non-invasively monitor the interaction of a cancer drug with its target in patients. With this work we hope to translate our knowledge about the biology of EGFR to a simple and clinically useful PET scan.”
PET imaging of the EGFR is accomplished by using a radiotracer called [11C]-erlotinib. Erlotinib is a drug that blocks activation of the EGFR, and potently blocks the growth of tumor cells with mutation of the EGFR. EGFR mutations are found in multiple cancers and come in many forms. Those with tyrosine kinase mutations, which activate the receptor’s activity, are the Yale team’s current focus. The radiolabeled form of erlotinib was planned and synthesized by a member of the team, radiochemist Yiyun Henry Huang, PhD, Professor of Radiology and Biomedical Imaging, and Co-Director of The Yale PET Center. Dr. Huang replaced one of the drug’s carbons with a radioactive carbon, which allows the compound to be traced by PET.
The team tested the technique by injecting [11C]-erlotinib into mice with lung cancer tumors harboring EGFR mutations. Evan Morris, PhD, Associate Professor of Radiology and Biomedical Imaging, Psychiatry, and Biomedical Engineering, and Co-Director of the PET Imaging Section, modeled the radiotracer’s distribution and the team was able to watch the drug bind to the tumor. This revealed the presence of the mutation and the effectiveness of the drug in blocking EGFR activity.
Their revelation could be a big step in the treatment of NSCLC, explained Dr. Contessa, because a physician Radiobiology and Radiotherapy RESEARCH PROGRAM can see whether the drug is hitting the target at every site in the body. If tumors are not imaged by [11C]-erlotinib PET, doctors can consider using another tyrosine kinase inhibitor or irradiating the sites missed by the drug. The technique can also reveal when patients are developing resistance to a drug, either generally or at certain sites, and hence could benefit from changing or supplementing their therapies. “We hope this technique will help physicians make these decisions earlier, by giving them more information more quickly,” said Dr. Contessa.
The next step, beginning now, is a Phase I trial with about two dozen patients at Smilow Cancer Hospital. That’s where the fourth member of the team comes in, medical oncologist Sarah Goldberg, MD, MPH, Assistant Professor of Medicine. “Dr. Goldberg is very interested in using this new technique to improve therapeutic decisionmaking for patients with EGFR mutations,” said Dr. Contessa.
The team believes this technique can be used for other types of cancer. “There are other tumor sites with specific mutations, and we might be able to develop radiotracers that specifically interact with those mutant proteins to give us a way to image different types of tumors,” said Dr. Contessa. “We think we can start to personalize imaging to find mutations, and use imaging as a way to gauge responses to therapy.”