The study, “Internalization Of Secreted Antigen–Targeted Antibodies By The Neonatal Fc Receptor For Precision Imaging Of The Androgen Receptor Axis,” describes a new cancer-specific antibody that can be tracked using positron emission tomography (PET) scans to provide real-time, accurate images of the tumor, and guide therapy.
Prostate cancer is typically diagnosed by assessing prostate-specific antigen (PSA) blood levels based on the theory that PSA levels are a measure of the androgen receptor pathway activation and cancer onset. However, PSA levels may change due to several factors, such as age and type of tumor, making it difficult to assess the real degree of androgen receptor activation. Also, as PSA circulates in the blood, it is not always clear which sites have been affected by the cancer, making it hard to track disease activity outside the prostate.
An international research team, led by David Ulmert, MD, at Memorial Sloan Kettering Cancer Center, developed an antibody called 11B6 that targets the hK2 protein. Like PSA, this protein reflects the activation of the androgen receptor, but has the advantage of being located specifically in the prostate.
Researchers observed that, when the antibody binds to the protein (11B6-hK2 complex), the complex enters cancer cells, allowing researchers to track down hK2-positive cancer cells.
The team then bound 11B6 to a radioactive molecule called zirconium-89, forming the complex 89Zr-11B6 and helping researchers trace the antibody with imaging techniques such as PET and fluorescence imaging. This way, when 11B6 binds to hK2, researchers can track and measure disease activity in the whole body, including bones, where prostate cancer sometimes metastasizes.
The value of the 89Zr-11B6 imaging method was tested in mice with prostate cancer to assess disease activity in patients who received treatment with Xtandi (enzalutamide), a drug used to treat prostate cancer by inhibiting the androgen receptor, and those who did not.
The team observed that, after castration, there was a decrease in the activation of the androgen receptor pathway, especially in mice treated with Xtandi.
“The findings show that individually tailored imaging agents can provide a unique way of looking at disease progression in real time and in a noninvasive manner,” Daniel Thorek, PhD, of Johns Hopkins Medicine and the lead author of the study, said in a news release. “Perhaps someday we can put a personalized antibody such as the one we created in our study on a therapeutic agent and conduct cancer treatment using imaging with very high specificity.”
The team believes the development of the 11B6 antibody may not only assist in the diagnosis of prostate cancer, but also guide treatments by helping achieve optimal drug dosages to ensure effectiveness while avoiding negative side effects, and determining the appropriateness of a given therapy.
Preliminary studies are currently being conducted by the team, a necessary step before applying for human clinical trials.