A newly developed molecular imaging technique can identify multiple subtypes of triple-negative breast cancer (TNBC), enabling earlier and more accurate detection of this aggressive disease, according to new research published in the June issue of The Journal of Nuclear Medicine. This approach has the potential to lead to better diagnosis, treatment planning, and monitoring for patients with TNBC.
TNBC is a heterogeneous disease, meaning it encompasses a wide range of different subtypes with varying biological behaviors and clinical outcomes. This makes it harder to identify, and as a result, TNBC lags behind other breast cancer types in targeted therapeutic and diagnostic imaging agent development.
“Noninvasive imaging is essential for diagnosing and staging TNBC and predicting and measuring treatment response,” says Jason Lewis, PhD, Emily Tow Chair at Memorial Sloan Kettering Cancer Center in New York. “In our study, we sought to overcome tumor cell marker heterogeneity by developing an imaging agent that could detect multiple TNBC subtypes and improve diagnostic capacity.”
Researchers targeted extra domain A of fibronectin (EDA-FN), a stable protein in the tumor stromal environment, which is abundantly expressed in breast cancer. A monoclonal antibody-based PET tracer ([89Zr]Zr-DFO-F8) was created to detect EDA-FN. This tracer was then evaluated in vitro and in vivo in several preclinical xenograft models of multiple TNBC subtypes.
[89Zr]Zr-DFO-F8 exhibited specific, blockable EDA-FN binding activity in vitro. In vivo experiments demonstrated high tumor uptake in preclinical TNBC xenograft models. [89Zr]Zr-DFO-F8 also detected EDA-FN in subcutaneous and orthotopic TNBC xenografts and accumulated in aggressive disease concordantly with EDA-FN expression.
“These findings highlight the potential of targeting extracellular matrix proteins to overcome tumor heterogeneity in imaging, offering improved diagnostic and therapeutic potential,” Lewis notes. “This approach paves the way for more universal, tumor microenvironment-based tracers in nuclear medicine and could expand precision imaging across diverse and hard-to-target cancers.”
— Source: Society of Nuclear Medicine and Molecular Imaging
New Combination Therapy Feasible for Neuroendocrine Tumors
A new combination therapy that pairs a radiopharmaceutical (177Lu-DOTATATE) with a DNA-repair blocker (olaparib) has been deemed feasible and tolerable for neuroendocrine cancer patients. The combined therapy works by preventing cancer cells from repairing themselves after targeted treatment and has the potential to help patients achieve longer-lasting disease control. This research was published in the May issue of The Journal of Nuclear Medicine.
177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is a mainstay strategy for low- to intermediate-grade metastatic neuroendocrine tumor patients. While this targeted radiopharmaceutical therapy provides long-term treatment effects—sometimes lasting for several years—ultimately, all patients will experience disease progression.
“In preclinical trials, PARP (poly[adenosine diphosphate–ribose] polymerase) inhibition has been identified as a promising strategy for enhancing PRRT efficacy,” says Andreas Hallqvist, MD, PhD, an associate professor, senior consultant, and head of the department of oncology at Sahlgrenska University Hospital in Gothenburg, Sweden. “Given its success, my colleagues and I sought to further explore this treatment strategy in the clinical setting.”
In the study, researchers combined 177Lu-DOTATATE PRRT with olaparib, a PARP inhibitor that increases the likelihood of tumor cell death by preventing effective repair of radiation-induced damage. Eighteen patients received 177Lu-DOTATATE PRRT followed by escalating doses of olaparib (50 to 300 mg twice a day) for up to four cycles. Toxicity was evaluated using National Cancer Institute Common Toxicity Criteria version 5.0. Time to progression, overall survival, response rate, and dosimetry variables were also measured.
The combination of 177Lu-DOTATATE and olaparib was generally well tolerated. Thrombocytopenia was the primary dose-limiting toxicity, observed in three patients at the 300 mg dose level. Other toxicities were mild, predominantly low-grade bone marrow suppression, nausea, and fatigue. At the six-month follow-up assessment, a 69% disease control rate was observed.
“Our study demonstrates the potential to further improve nuclear medicine by combining targeted radiotherapy with drugs that increase the efficacy,” Hallqvist says. “This paves the way for smarter, more personalized cancer treatments. It’s our hope that more patients can receive the benefits from nuclear medicine, such as this combined therapy, in the future.”
— Source: Society of Nuclear Medicine and Molecular Imaging