Non-invasive Ovarian Cancer Detection & Treatment with Novel Radiotheranostic System

A novel radiotheranostic apparatus possesses the capability to noninvasively detect and address ovarian cancer, as per recent research disclosed in the April edition of The Journal of Nuclear Medicine. By merging the highly targeted huAR9.6 antibody with PET and therapeutic radionuclides, this theranostic framework holds promise for delivering tailored treatment, thus enhancing the prognosis for ovarian cancer patients.

This cancer accounts for more fatalities than any other gynecological malignancy, boasting a dismal five-year survival rate of under 30 percent for individuals diagnosed at advanced stages. The prevailing standard protocol for ovarian cancer entails surgical intervention followed by platinum-based chemotherapy. Nevertheless, these modalities have proven inadequate in bolstering overall survival rates due to tumor recurrence and the emergence of chemoresistance.

“Current serum-based biomarkers do not sufficiently detect all occurrences of early-stage ovarian cancer. Therefore, there is a critical need for both additional detection methods and new targeted therapies that can improve patient survival.” – Jason Lewis, PhD, Chief Attending of Radiochemistry and Emily Tow Chair at Memorial Sloan Kettering Cancer (MSK) in New York, New York

Research has elucidated that the MUC16 protein exhibits heightened expression in ovarian cancer patients, with escalated levels correlating intricately with disease progression and tumor dimensions. The antibody huAR9.6 attaches to a distinct epitope modulated by truncated carbohydrate residues on MUC16. Consequently, the authors observed that MUC16 holds promise as a plausible target for tumor detection through immuno-PET imaging and subsequent radioimmunotherapy.

The investigation scrutinized the diagnostic radiotracer 89Zr-DFO-huAR9.6 both in vitro and in vivo, encompassing binding assays, immuno-PET imaging, and biodistribution analyses using ovarian cancer murine models. Furthermore, ovarian xenografts were employed to ascertain the safety and efficacy of the therapeutic radionuclide, 177Lu-CHX-A″-DTPA-huAR9.6.

Immuno-PET imaging successfully detected MUC16 proteins using 89Zr-DFO-huAR9.6. In vivo assessments revealed the proficiency of 89Zr-DFO-huAR9.6 in delineating varying MUC16 expression levels in ovarian cancer murine models. Radioimmunotherapy trials with 177Lu-CHX-A″-DTPA-huAR9.6 showcased enhanced overall survival and robust antitumor responses in models exhibiting high MUC16 expression. Transient hematologic toxicity was also identified in mice subjected to 177Lu-CHX-A″-DTPA-huAR9.6 treatment.

“Employing this radiotheranostic duo for immuno-PET imaging of MUC16 may enable noninvasive diagnosis and treatment monitoring of lesions in patients with ovarian tumors,” remarked Kyeara Mack, PhD, postdoctoral researcher in the Lewis Laboratory at MSK. “Moreover, this theranostic platform holds potential for stratifying and identifying patients who stand to gain from targeted radioimmunotherapy. Additionally, it could play a pivotal role in the early detection of ovarian cancer.”

For more information: Interrogating the Theranostic Capacity of a MUC16-Targeted Antibody for Ovarian Cancer, Society of Nuclear Medicine and Molecular Imaging, https://doi.org/10.2967/jnumed.123.266524