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Meet the Investigator

February 07, 2019
by Jane E. Dee

In the Positron Emission Tomography (PET) Center’s newest lab, Bernadette Marquez-Nostra, PhD, is developing new PET imaging agents that can be used in precision medicine to target cancer cells.

Marquez-Nostra’s research could ultimately result in the use of PET imaging to select patients who might benefit from antibody therapies noninvasively, without the need for a biopsy.

“My focus is to evaluate the imaging agent and the therapy together in preclinical studies to test whether imaging can predict response to therapy. I’m looking at new targets for triple negative breast cancer that people haven’t imaged before because this type of cancer needs new targets for therapy. PET imaging has the potential to help select patients who might benefit from new targeted treatments,” Marquez-Nostra said.

Marquez-Nostra, an assistant professor in the Department of Radiology & Biomedical Imaging at Yale School of Medicine (YSM), also is establishing a clinical trial in her Cancer Imaging and Therapeutics lab to visualize response to immunotherapy in melanoma and renal cell carcinoma.

“Melanoma is one of the fastest-growing cancer diagnoses in the United States and is a cancer that commonly affects young patients,” said Rob Goodman, MB BChir, chair of the Radiology & Biomedical Imaging Department at YSM. “This makes the development of new imaging agents so critical for patients with this disease.”

Marquez-Nostra is collaborating on this trial with Darko Pucar, MD, an associate professor in the Nuclear Medicine section of the Radiology & Biomedical Imaging Department at YSM; Sarah Weiss, MD, Harriet Kluger, MD, and Marcus Bosenberg, MD, PhD of Yale Cancer Center; Richard Carson, PhD, director of the Yale PET Center, Henry Huang, PhD, co-director of the PET Center, and Chi Liu, PhD, associate professor of the PET Center.

“We were very excited to recruit Dr. Marquez-Nostra to the PET Center. Her novel translational oncology PET imaging using labeled antibodies and other ‘biologics’ complements our ongoing small-molecule PET tracer development efforts, led by Dr. Henry Huang,” said Carson, the PET center’s director.

Marquez-Nostra added that with continued research and clinical trials, “the better we can show how predictive PET scans can be, not just in detecting where cancer is, but to really predict if the drug that’s going to be used will go to the tumor.”

A ‘First’

“We were the first group to image the glycoprotein non-metastatic melanoma B (gpNMB) in the body, a transmembrane protein that is mostly present on the surface of cancer cells while present inside normal cells. This gives a unique opportunity to deliver drugs selectively to cancer cells and save normal cells from toxicity,” Marquez-Nostra said. “Now we’re trying to understand what role gpNMB has in cancer, particularly in triple negative breast cancer, and whether it’s a good target to go after for treatment.” she said.

“The standard way to look at the expression of gpNMB in tissue is to take a biopsy and stain the tissue for gpNMB.”

Her team is able to image gpNMB “because we tagged an antibody that binds to it with Zirconium-89, the signal that we see in PET,” she explained. “At the same time, we’re also imaging where the antibody is going in the body, so we have an idea how much of the antibody goes to the tumor and how much goes everywhere else. And we know gpNMB is in the tumor because we confirmed it with the standard method of detecting antigens on tissue.”

Marquez-Nostra began her gpNMB research as a postdoc at Washington University in St. Louis, Missouri.

“Antibodies are commonly used in cancer therapeutics because of their high affinity and

specificity for their antigens, inhibiting various molecular pathways in cancer or modulating immune responses to kill cancer cells,” she said. “Additionally, antibodies are robust and can be

modified with toxic payloads or therapeutic radionuclides to increase potency while reducing

toxicity. We are currently evaluating the efficacy of these biomolecules in preclinical models of breast cancer and melanoma.”

The Cancer Imaging and Therapeutics lab consists of laboratories for tissue culture, radiochemistry, and production of radiopharmaceuticals for human use. Marquez-Nostra is assisted by Alessandra Cavaliere, a postdoctoral associate with a PhD in medicinal chemistry and radiochemistry, and Supum Lee, a research assistant.

Submitted by Angel Machon on February 07, 2019