Using Form and Function to Detect and Treat Cancers
Detecting and monitoring cancer through imaging has made great strides over the decades in an effort to reduce invasive biopsies or surgeries. Imaging procedures, such as CT (computerized tomography) or MR (magnetic resonance) scans are useful to visualize tumor formations at specific sites inside the body.
However, those imaging techniques are limited in identifying how the tumor functions – an area in which PET (positron emission tomography) scans excel.
“One thing someone can ask is, ‘If you have CT and MR, why do you need PET imaging?’” said UW Carbone Cancer Center member and nuclear medicine physician Steve Cho, MD. “We’re looking at the processes of things, and it opens your eyes to see tumors that are very difficult to find or for which the primary site is unknown.”
Cho researches ways to improve PET imaging primarily for prostate cancer, but his work has helped improve PET scans for many different types of solid tumors.
“You have a radioactive substance which you inject into patients, and it will bind to its specific targeted receptor on the cancer cells and then light up that specific process in a PET image,” Cho said. “We can look at these hot spots to stage a patient’s cancer, to see if the cancer has spread outside the primary area or to determine if a tumor is being treated appropriately or not.”
For nearly two decades, clinicians have been using a radiolabeled version of the sugar, glucose, to light up tumors, because tumors require more energy to grow and thrive compared to healthy tissue.
“However, certain tumors don’t take up the glucose analog well, limiting current PET applications,” Cho said. “One example is prostate cancer. So there’s been a lot of work to get new radiotracers to fill this void.”
Cho and colleagues at UW Carbone and across the country are working to improve one agent, prostate specific membrane antigen (PSMA). PSMA binds to a receptor found on prostate cells, and there is an effort to bring PSMA-PET imaging agents to the clinic. For example, the current imaging techniques used for metastatic prostate cancer patients is primarily CT and bone scans. However, those scans have limited sensitivity to localize where the cancer has spread.
“As a patient’s PSA prostate cancer marker levels rise, you image with CT or bone scan to find the cancer. If the scan is negative, then you assume the cancer has recurred in the surgical prostate bed and treat that area, then wait to see if the PSA levels fall,” Cho said. “However, there may be recurrent metastatic disease outside of the prostate bed. So probably the largest clinical scenario for this agent is to image these patients with this more sensitive PSMA-PET scan to better and more accurately detect metastatic disease in order to treat the patient appropriately.”
Another important area of Cho’s research is in theranostics, or combination diagnostic and therapeutic agents. A recent example of a theranostic, that Cho and colleagues helped bring to University Hospital with other colleagues in nuclear medicine and GI oncology, is for the diagnosis and treatment of neuroendocrine tumors. Most neuroendocrine tumor cells have a receptor on their surface that can be targeted with a specific molecule.
“You use the same cancer-targeting molecule, and either attach the PET imaging radiolabel to detect the cancer and monitor treatment progress, or the therapeutic radiolabel to kill the tumor cells,” Cho said. “The neuroendorcrine tumor example is a pioneering theranostic agent for cancer treatment, and we have an overall goal of heading in that direction with theranostic agents in the prostate cancer field and many other cancers."
And while prostate cancer is the only cancer type that has the receptor for PSMA-PET, it is also expressed by the blood vessels of several other tumors. Cho is working to translate that finding in with gynecologic oncologist Lisa Barroilhet, MD and radiologist Liz Sadowski, MD, to pilot a clinical trial for early detection of gynecological cancers. He is also working with bioengineer David Beebe, PhD, urologist Jason Abel, MD and genitourinary oncologist Christos Kyriakopoulos, MD in another PSMA-PET clinical trial for renal cell cancer.
“With this one target, we are trying to do a number of different things,” Cho said. “The hope is to try to apply this theranostic paradigm to many other types of PET agents for many other types of cancers.”
Date Published: 05/08/2018