Novel Theranostic Model Shows Curative Potential for Gastric and
Pancreatic Tumors
Reston,
VA (January 13, 2026)--A newly developed radiopharmaceutical pair can
precisely detect and effectively treat--completely eradicating tumors in certain
preclinical models--gastric and pancreatic tumors. Targeting the well-defined
and accessible biomarker claudin-18.2, the theranostic technique has the
potential to move the field substantially closer to durable disease control and
potentially cure--in otherwise difficult-to-treat solid tumors. This research
was published in the January issue of The Journal of Nuclear Medicine.
Advanced upper gastrointestinal cancers,
including esophageal, gastric, and pancreatic cancer, are among the deadliest
cancers worldwide, accounting for one-third of all cancer deaths. Patients have
very limited treatment options, especially in advanced stages, and current
therapies provide only modest improvements in survival. As such, there is a
critical unmet need for more effective and more precise approaches.
"Claudin-18.2 recently gained clinical
attention following U.S. Food and Drug Administration approval of the gastric
cancer treatment zolbetuximab, which targets the
biomarker," said Shadi Esfahani, MD, MPH, nuclear medicine physician at
Massachusetts General Hospital in Boston. "To further explore the utility of
claudin-18.2, my colleagues and I developed a first-in-class
claudin-18.2-targeted PET radiopharmaceutical and a therapeutic counterpart to
identify and treat gastric and pancreatic tumors."
To evaluate the theranostic pair, preclinical murine models were developed with
both pancreatic and gastric cancer cell lines. Serial PET imaging with 89Zr-DFO-zolbetuximab
or 89Zr-DFO-IgG as a control was performed at one, three, and six
days, followed by ex vivo analysis of biodistribution. Next, tumor-bearing mice
received a single intravenous injection 177Lu-DOTA-zolbetuximab
(high or low dose), non-radiolabeled zolbetuximab, 177Lu-DOTA-IgG,
177Lu-DOTA, or saline as a treatment. Effectiveness and toxicity of
the treatments were evaluated by laboratory and histologic analyses.
Serial PET imaging demonstrated a high tumor uptake of 89Zr-DFO-zolbetuximab
at all timepoints--significantly higher than the uptake seen in mice imaged with
control 89Zr-DFO-IgG. High-dose 177Lu-DOTA-zolbetuximab
resulted in reduced tumor growth in gastric and pancreatic mice models, with
complete regression of most pancreatic tumors. No radiation-induced toxicities
were observed during the study.
"Claudin 18.2 based theranostics could meaningfully change patient care in two
important ways," noted Esfahani. "First, claudin 18.2 targeted PET imaging
enables noninvasive identification of patients whose tumors strongly express
this target. Second, claudin 18.2 targeted radiopharmaceutical therapy has the
potential to deliver highly focused radiation directly to tumor cells, leading
to significant tumor shrinkage and the possibility of improved survival."
She continued, "More broadly, the study underscores how advances in biomarker
discovery, radiopharmaceutical development, and patient selection are bringing
the field closer to treatments with curative potential rather than incremental
benefit. As additional tumor-specific targets are identified and validated,
molecular imaging-guided theranostics could increasingly enable personalized,
highly effective, and safer cancer treatments, positioning nuclear medicine at
the forefront of next-generation oncology."