A novel radiopharmaceutical pair has demonstrated that it can detect and effectively treat gastric and pancreatic tumors, completely eliminating tumors in some preclinical models.
The newly developed theranostic approach targets the well-defined and accessible biomarker claudin-18.2, according to research from a team including Shvan Raheem, PhD, at Massachusetts General Hospital (MGH) and Harvard Medical School, both in Boston, and Shadi Esfahani, MD, also of MGH. Their findings have been published in the January issue of the Journal of Nuclear Medicine.
There is a critical unmet need for more precise and effective treatments for advanced upper gastrointestinal cancers, for which treatment options are limited, providing only modest improvement for patients, the authors noted. They developed preclinical murine models to evaluate the approach with both pancreatic and gastric cancer cell lines. Serial PET imaging with zirconium-89 desferrioxamine zolbetuximab (Zr-89 DFO-zolbetuximab) or Zr-89 DFO-immunoglobulin G (IgG) as a control was performed at one, three, and six days, followed by analysis of biodistribution. The tumor-bearing mice then received a single intravenous injection of lutetium-177 (Lu-177) DOTA-zolbetuximab (high or low dose), nonradiolabeled zolbetuximab, Lu-177 DOTA-IgG, Lu-177 DOTA, or saline as a treatment.
Serial PET imaging showed that tumor uptake of Zr-89 DFO-zolbetuximab at all timepoints was significantly higher than the uptake seen in mice imaged with the control Zr-89 DFO-IgG. High-dose Lu-177 DOTA-zolbetuximab resulted in reduced tumor growth in both the gastric and pancreatic mouse models, with most of the pancreatic tumors showing complete regression.
Importantly, there were no radiation-induced toxicities during the study, further confirming the utility of the claudin-18.2-targeted theranostic pair, the team reported.
Read the study here.
