SAN ANTONIO – Early clinical studies of radiopharmaceutical imaging agents have suggested they could be able to diagnose metastatic breast cancer, characterize tumor biology, and track treatment response.
The research, presented at the San Antonio Breast Cancer Symposium last week, featured imaging agents designed to detect HER2 and PARP expression on cancer cells. Researchers tested how well these radiopharmaceutical agents could diagnosis breast cancer subtypes, pick up intratumor biomarker heterogeneity, and monitor patients' chemotherapy response.
Farrokh Dehdashti, professor of radiology at Washington University in St. Louis, noted that these imaging biomarkers could potentially help improve patient management on several fronts.
"Systemic therapy of breast cancer is based on the biomarkers of tumor tissues that is evaluated by in vitro assays," Dehdashti, who was not involved with the research, said in a discussion of the data from these studies at the meeting. "However, not every patient responds to these therapies, and they're associated with various degrees of toxicity."
She added that the field needs patient management tools that can enable better individualized therapy through improved staging and therapy response prediction.
Detecting metastatic disease
Australia-headquartered imaging firm Imagion Biosystems evaluated the ability of its MagSense HER2 agent to detect axillary lymph node metastasis in HER2-positive breast cancer patients who have suspicious nodes by conventional imaging.
The MagSense HER2 imaging agent is an anti-HER2 molecule conjugated with magnetic iron oxide nanoparticles. Imagion CEO Isaac Bright presented data at the meeting from a 13-patient Phase I study, which confirmed that this agent is detectable by MRI and pathology assessments and that it drains into the lymph nodes.
In scans after the MagSense HER2 agent was administered to patients, radiologists observed a distinct and differentiable MRI appearance in morphologically normal and suspicious nodes, which independent radiologists confirmed in a blinded review.
Normal lymph nodes had homogeneous hypointensity on MRI scans, while morphologically suspicious nodes showed partial irregular darkening or speckled heterogeneous hypointensity. The suspicious nodes that were biopsied confirmed the presence of HER2-positive nodal metastasis.
"MRI assessment of [MagSense HER2] imaging performed similar to or better than standard-of-care axillary ultrasound imaging," Bright said.
In her review of the data, Dehdashti agreed that this agent showed it could evaluate HER2 status of the metastatic region noninvasively, and "hopefully in the future, may lead to less biopsies and facilitate the start of the therapy [earlier]," she said.
HER2 subtyping
In another Phase II clinical trial, researchers assessed whether the [89Zr]trastuzumab PET and MRI imaging agent could diagnose HER2-positive breast cancer and determine HER2 expression heterogeneity in tumors without the need for a biopsy. Ameer Mansur, a graduate research fellow at the University of Alabama, Birmingham, presented results at the meeting on Wednesday from 13 patients.
Mansur and colleagues used both PET imaging and diffusion-weighted MRI in the trial to characterize breast tumors and HER2 expression. The addition of MRI, they hypothesized, may improve breast imaging due to its higher sensitivity in soft tissues.
With PET-MRI imaging, the researchers generated apparent diffusion coefficient maps to characterize intratumoral heterogeneity in HER2 expression. "These maps allow for generation and identification of subregions that are biologically distinct within the tumor and can allow evaluation of treatment response or even [provide] follow-up guidance for biopsies," Mansur said.
Dehdashti noted in her discussion that heterogeneity in HER2 expression within a tumor is important to identify because it is often an indicator of a poor prognosis, pointing to the need for more aggressive treatment.
The uptake of [89Zr]trastuzumab was higher overall in tumor cells compared to normal cells. The [89Zr]trastuzumab PET images also showed that lesions in the brain and lymph nodes had intratumoral heterogeneity of HER2 expression that would have been more difficult to identify with a biopsy, Mansur said.
The researchers also found that one of the five patients with a breast lesion, who had previously completely responded to HER2-targeted therapy, exhibited the highest uptake of the agent in the tumor.
"[89Zr]trastuzumab PET-MRI could enable for noninvasive evaluation of HER2 expression and intratumoral cellularity," Mansur said. "We are currently conducting an assessment of correlation between the imaging metrics and treatment response kinetics to assess the prognostic capabilities of this modality."
Predicting chemo response
Researchers from the University of Pennsylvania explored the ability of [18F]FluorThanatrace, or [18F]FTT for short, an 18F-labeled PARP inhibitor analog that binds to the same site as approved PARP inhibitor drugs, to predict which breast cancer patients would respond to chemotherapy using PET imaging.
The researchers tested the PARP imaging agent in the neoadjuvant setting. Patients received the [18F]FTT agent and a PET scan prior to beginning their chemo regimen and then were followed through their surgery and evaluated subsequently for response.
Sarah Gitto, an instructor of pathology and laboratory medicine at the University of Pennsylvania, who presented the results at the meeting, said previous research has showed this agent can also predict ovarian cancer patients' response to PARP inhibitors.
The Phase I study included 26 patients with a range of breast cancer subtypes, including estrogen receptor-positive, HER2-negative; HER2-positive; and triple-negative breast tumors. Gitto and colleagues found that pre-treatment uptake of [18F]FTT in triple-negative breast cancer patients was higher among those who went on to have a pathological complete response to chemo. Across all subtypes, there was a trend of higher uptake associated with chemo response.
Data from the published "literature suggests that defective DNA damage repair may have a potential vulnerability to chemotherapy in triple-negative breast cancer, supporting these results," Gitto said. "FTT PET imaging may predict response to neoadjuvant chemotherapy in breast cancer, and further study evaluating this as well as PARP expression as a biomarker for chemotherapy response is warranted."