A new theranostics pairing of molecular imaging targeting somatostatin receptor 2 (SSTR2) and radioligand therapy with SSTR2-targeted actinium-225 (Ac-225) DOTATATE shows promise as a therapeutic option for patients with metastatic breast cancer.
A team led by Gary Ulaner, MD, of the University of Southern California in Los Angeles reported that SSTR2-targeted therapy with alpha-emitting Ac-225 DOTATATE showed a "near complete response in a heavily pretreated participant with metastatic ER-positive breast cancer and a Krenning 4 DOTATATE PET result." (The Krenning score system is used to assess the degree of tracer uptake in tumors, with 0 equal to no uptake and 4 equal to uptake comparable to or higher than the spleen.) The group's findings were published July 30 in Radiology.
Researchers have associated somatostatin receptors -- specifically SSTR2 -- mainly with neuroendocrine tumors and tracking their uptake has revolutionized the imaging and therapy of patients with these tumors, the team explained. SSTR2 is expressed on other tumors at lower prevalence; Ulaner and colleagues explored whether it would be expressed in patients with metastatic breast cancer and whether this result could offer an SSTR2-targeted imaging and therapy option.
The group conducted a study that included 30 women with metastatic ER-positive breast cancer who were recruited to a phase 2 SSTR2-targeted imaging trial and underwent DOTATATE PET/CT between January and August 2023.
The study found that DOTATATE PET/CT showed that nine of 30 participants (30%) had tumors with Krenning scores of 3 or 4, "indicating strong SSTR2 expression." In fact, preclinical microarrays demonstrated that 51% of ER-positive breast cancer tissue samples showed SSTR2 uptake compared to 18% of ER-negative breast cancer tissue samples (p < 0.001). Of the 30 women, one had treatment with SSTR2-targeted actinium 225 DOTATATE, the team reported.
Although the research is limited by the fact that only one patient was treated, "the case is instructive in several ways," wrote Frank Lin, MD, and Peter Choyke, MD, both of the National Cancer Institute in Bethesda, MD, in an accompanying commentary.
"[The study] draws attention to the expression of SSTR2 in breast cancer, especially in ER-positive tumors [and] demonstrates that SSTR2-targeted imaging can help guide decisions to use SSTR2 radioligand therapy … it shows that α-based Ac-225 DOTATATE, although not yet approved by the [U.S. Food and Drug Administration], has potential for dramatic responses in at least some selected patients. [The] results will hopefully encourage clinician-scientists who treat metastatic breast cancer to consider studying SSTR2-targeted therapies in prospective clinical trials."
The complete study can be found here.
