Phillip Kuo, MD, PhD

Recently, personalized medicine has made important advances. Two targeted therapeutics, Roche’s Zelboraf, also called vemurafenib, for late-stage skin cancer and Pfizer’s Xalkori, or crizotinib, for late-stage non-small-cell lung cancer, were FDA approved, as well as their corresponding companion diagnostics, which are tests that identify whether the patient expresses the biomarker the therapeutic is targeting. The approval of these drugs is a prime example of personalized medicine, as only the patients identified using the companion diagnostic as expressing a specific biomarker will receive the targeted drug.

As interest in personalized medicines continues to surge, radiologists will play an increasingly important role in using imaging-guided companion diagnostics to deliver this personalized care.

While typical tests identifying biomarkers use a biopsy or a blood draw, such as the prostate-specific antigen study used in prostate cancer screening, interest in using imaging diagnostics to identify biomarkers is increasing. These imaging biomarkers are increasingly being recognized by clinical scientists, industry researchers and regulatory bodies such as the FDA as suitable parameters around which to design clinical trials, which will lead to their increased use in the clinic and practice.

The trend of the use of companion imaging diagnostics has been seen most prevalently in cancer treatment, where these tests have advanced the furthest. These companion diagnostics are often called theranostics, as the tests are used to guide treatment of the patient.

Companion diagnostics based on imaging agents have many advantages, including the ability to visualize the expression of a molecular marker on a lesion and elimination of biopsy bias that can arise when a single patient has both positive and negative lesions. The ability to visualize lesions in real time is also important in light of recent studies that have shown biomarkers in metastatic sites can vary and change over time, which may be overlooked by relying on a biopsy.

With the use of a companion imaging diagnostic, the patient’s whole body can be imaged non-invasively, enabling a comprehensive understanding of biomarker expression on a tumor to be achieved. In addition, companion imaging diagnostics commonly rely on PET and SPECT imaging, which are technologies used in the clinic today, and thus are easily adapted into practice by the medical community.

Current approaches for companion imaging agents that assess the expression of certain disease-related biomarkers are focused on the use of antibody-based PET and SPECT imaging, which combine the targeting antibody or antibody-fragment with different radioisotopes. This combination results in a balance between the physical half-life of the radioisotope with the pharmacokinetic half-life of the antibody, creating an effective diagnostic.

Another promising approach is the use of small molecules conjugated to an imaging agent, which is being advanced by Endocyte. Their companion imaging agent based on this approach, etarfolatide, identifies patients that overexpress the folate receptor and is paired with a drug that targets the folate receptor, vintafolide, which consists of a small molecule linked to a chemotherapy drug. Etarfolatide is currently in Phase 3 study in platinum-resistant ovarian cancer, and is under review for conditional approval in the EU for the same indication, along with vintafolide.

As personalized medicine continues to advance, interest in developing companion imaging diagnostics will only continue to grow, and these approaches are advancing in the clinic and in some cases have arrived at the radiologist’s practice. The use of imaging agents for personalized medicine has many advantages, including the ability to image the whole body, which will ultimately translate to benefits for patients.

Phillip Kuo, MD, PhD, is associate professor of radiology, medicine and biomedical engineering; nuclear medicine section chief; and director of PET/CT at the University of Arizona. He is also a consultant for Endocyte.

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There’s growing interest in companion imaging diagnostics for personalized care. Using imaging agents for personalized medicine ultimately benefits patients.

Phillip Kuo, MD, PhD

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