March/April 2026 Issue

Small but Mighty
By Beth W. Orenstein
Radiology Today
Vol. 27 No. 2 P. 18

Advanced imaging and interventional innovations aim to improve pancreatic cancer outcomes with nanoparticles.

Pancreatic cancer remains one of the most lethal cancers, with a five-year survival rate of about 13%, according to the Pancreatic Cancer Action Network. Outcomes remain poor largely because the disease is often diagnosed at an advanced stage. The pancreas sits deep in the abdomen, allowing tumors to grow for months with few noticeable symptoms. By the time the cancer is discovered, it has often spread to nearby blood vessels or organs. This makes surgery technically difficult—and, in many cases, not feasible.

Moreover, pancreatic cancer has historically been resistant to standard treatments. While chemotherapy can slow pancreatic cancer, it rarely eliminates it completely, and side effects can be severe because the treatment is not very selective. Radioligand therapy is more selective than chemotherapy, but it still affects everything in its path. Radiation has been shown to shrink pancreatic tumors, but complete responses in pancreatic cancer are uncommon.

Within this difficult landscape, two recent animal studies are drawing attention. Both explore new ways to more precisely detect and treat pancreatic cancer and potentially other upper gastrointestinal cancers, as well.

A New Approach
In a study published in January 2026 in the Journal of Nuclear Medicine, researchers at Harvard University describe a new theranostic approach—a strategy that combines diagnostic imaging with targeted treatment. The work focuses on pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, as well as gastric and gastroesophageal junction cancers.

“Our studies show promise particularly for gastric adenocarcinoma, gastroesophageal junction adenocarcinoma, and pancreatic ductal adenocarcinoma, the most common malignancies within their respective organ systems,” says lead author Shvan J. Raheem, PhD, a postdoctoral fellow in the lab of nuclear medicine physician Shadi Esfanai, MD, MPH, at Massachusetts General Hospital and Harvard Medical School in Boston.

The researchers developed what they call a radiopharmaceutical pair—two closely related drugs built around the same targeting antibody. One is used for PET imaging to locate tumors in the body. The other delivers radiation directly to cancer cells. Their work showed that in preclinical mouse models, the imaging agent clearly highlighted tumors while the therapeutic version significantly reduced tumor size. Pancreatic tumors showed complete regression at higher treatment doses. Importantly, no treatment-related toxicities were reported in the study, Raheem says.

The approach centers on a protein called Claudin 18.2 (CLDN18.2). In healthy tissue, CLDN18.2 is tucked away within tightly connected cells that line parts of the stomach and digestive tract. These tight junctions act like seals between cells, helping maintain tissue integrity. Previous researchers have described the cell membranes as appearing to “kiss” at these claudin tight junctions when looking at them under the microscope.

Building on that description, Raheem says these “hot kisses” (with “hot” referring to the tight therapeutic radionuclide and “kisses” to the tightjunction contact points) may offer a promising strategy for treating tumors that express high levels of CLDN18.2. In cancer, this orderly structure of tightly connected cells breaks down. The protein becomes exposed on the surface of tumor cells and overexpresses, making it accessible to targeted drugs.

“That differential accessibility is what makes CLDN18.2 such an attractive target,” Raheem says.

Using a PET tracer made by attaching zirconium-89 to the antibody zolbetuximab, the researchers were able to noninvasively map where CLDN18.2 was expressed throughout the body. For treatment, they labeled the same antibody with the radioactive isotope lutetium-177, allowing it to deliver radiation directly to tumors expressing the protein. Together, the approach follows what Raheem describes as the theranostic principle of “see what you treat, treat what you see.”

Gaining Attention
CLDN18.2 has already gained attention in clinical oncology. In October 2024, the FDA approved zolbetuximab for certain gastric cancers that express the biomarker. Building on that momentum, Raheem and colleagues developed what they describe as a first-in-class CLDN18.2-targeted PET imaging agent, along with a therapeutic counterpart to identify and treat gastric and pancreatic tumors.

One long-standing challenge in pancreatic cancer imaging has been specificity. Some imaging agents accumulate in normal tissue or in inflammatory conditions such as pancreatitis, leading to false positives and limiting how aggressively therapy can be delivered.

“This is where CLDN18.2 really stands out,” says Cathy Cutler, PhD, director of the Medical Isotope Research Production and Development group at Brookhaven National Laboratory, commenting on this research.

In preclinical models, uptake in normal tissues was extremely low to nonexistent. “That’s a major accomplishment,” Cutler says. “Low normal tissue uptake lowers false-positive rates for imaging and reduces toxicity for therapy, which allows for more efficient dosing.”

Promising Results
That level of precision may be especially important in the most common form of pancreatic cancer, PDAC, which frequently grows around sensitive blood vessels and organs and is often considered unresectable at diagnosis. Lower background uptake could also allow the use of radioisotopes that travel shorter distances in tissue, potentially improving tumor control while sparing nearby healthy structures, Raheem says.

If these findings translate to humans, CLDN18.2-based radiotheranostics could influence care in several ways. Whole-body PET imaging could improve patient selection and treatment planning by reducing the sampling errors that can occur with a single biopsy, Raheem says. The matched therapeutic agent could then deliver high doses of radiation directly to tumors while minimizing damage to normal tissue.

Currently, eligibility for CLDN18.2-targeted immunotherapy depends on strict immunohistochemistry criteria—moderate to strong staining in at least 75% of tumor cells. That requirement limits treatment to roughly 40% of patients with HER2-negative gastric and gastroesophageal junction cancers. In the mouse studies, however, tumors with lower levels of CLDN18.2 expression, between 41% and 74% of cells, still responded to a single dose of lutetium-177–labeled zolbetuximab with significant tumor growth inhibition and improved survival compared with the nonradioactive antibody.

Raheem suggests that radiopharmaceutical therapy may eventually broaden eligibility. Lowering the positivity threshold to more than 25% could potentially expand access to as many as 75% of patients, he says. Whether such targeted radiopharmaceuticals could one day replace major surgery, such as the Whipple procedure for pancreatic cancer, remains uncertain.

“It’s too early to say,” Raheem says. “But targeted radiopharmaceuticals can potentially be integrated at multiple points along the treatment pathway, either as primary therapy in advanced disease or as an adjunct in earlier stages.”

While Cutler believes the research is promising, she emphasizes caution. Imaging demonstrated high and specific tumor uptake that increased over several days, and a single, nonoptimized therapeutic dose produced significant tumor regression and improved 90-day survival with a favorable safety profile. “The fact that this worked in a proof-of-concept study speaks to its potential,” she says.

The Body Electric
A second innovative strategy comes from researchers at Sylvester Comprehensive Cancer Center at the University of Miami, in collaboration with Moffitt Cancer Center and Cellular Nanomed. Their approach uses magnetoelectric nanoparticles (MENPs)—tiny, engineered particles that respond to magnetic fields.

Originally developed in the laboratory of Sakhrat Khizroev, PhD, at the University of Miami, in collaboration with Ping Liang, PhD, of Cellular Nanomed, the technology allows nanoparticles to be injected into the bloodstream, guided toward tumors using external magnets, and then activated remotely to destroy cancer cells. The particles also provide imaging capabilities, allowing researchers to monitor the treatment in real time. In their November 2025 study in Advanced Science, the team demonstrated that MENPs could be steered to pancreatic tumors in animal models and activated to eliminate cancer cells without the need for traditional drugs.

“This study brings us one step closer to connecting the human body wirelessly to help it heal in real time,” says Khizroev, a professor of electrical and computer engineering at the University of Miami. “We hope it opens a new era in medicine where technology can precisely target diseases that were once considered untreatable.”

Like the CLDN18.2 radiotheranostic approach, the nanoparticle strategy aims to concentrate treatment at the tumor site rather than exposing the entire body to therapy. It is fundamentally different from drugs or radiation. It uses tiny particles injected into the bloodstream that are switched on by an MRI’s magnetic field. When activated, the particles create extremely localized electric effects only where they touch cancer cells, triggering the cells’ natural self-destruct process.

Cancer cells have distinct electrical properties (membrane potential, conductivity, dielectric properties) compared with healthy cells, Khizroev explains. “According to our prior comprehensive numerical simulations, this difference allows MENPs to selectively target cancer cells, addressing one of oncology’s biggest challenges: specificity without harming normal tissue,” he says.

The researchers chose pancreatic cancer because it is among the hardest-to-treat cancers and is poorly responsive to chemotherapy, radiation, and even immunotherapy, Khizroev says. Collaboration with the Moffitt Cancer Center, a National Cancer Institute-designated center, was pivotal in advancing their pancreatic cancer studies, he notes.

Acting Locally
Electric fields control biology at the molecular level, but you can’t control electric fields wirelessly in the body. “Magnetic fields can,” Khizroev says. “That insight changed everything.”

Traditional electric-field cancer treatments such as electroporation are effective, but they require dangerously high electric fields applied over large areas, risking damage to nearby organs, Khizroev says. MENPs replicate the benefits of electroporation and other electric field effects but act locally at the nanoscale, are wirelessly controlled, and avoid large-scale tissue damage.

“Our experiments indicate that the treatment causes cancer cell membranes to rupture, releasing intracellular contents, which in turn is believed to trigger a powerful immune response,” Khizroev says. He describes it as “immunotherapy on steroids.” It is possible that the immune system gets fully activated after the cancer cells are destroyed, he adds.

In their mouse models, the researchers saw complete tumor ablation and impressive survival rates. In about one-third of cases, tumors were erased completely. And in some cases, a single treatment (“one shot”) was sufficient, they note.

“The survival rates were unprecedented,” Khizroev says.

The researchers saw no detectable organ damage. “We don’t use drugs or biomolecules. This is a purely physical mechanism, which dramatically reduces side effects,” Khizroev says. Also, they believe, their approach not only eliminated bulk tumor cells but also likely destroyed cancer stem cells, which reduces recurrence risk, Khizroev says.

The approach is highly controllable and tunable at the molecular level, he adds. It does not require specialized imaging equipment (ie, special MRI systems) to function. However, he says, the nanoparticles are extraordinarily difficult to make—they are 10 to 30 nanometers wide, engineered with atomic precision.

After more than 10 years of foundational research, the technology is considered “fully tuned,” Khizroev says. He says the barriers to commercialization that remain are largely regulatory and bureaucratic. Khizroev expects clinical trials could start in one to two years, depending on approvals. The company, Cellular Nanomed, has been cofounded to scale up manufacturing of MENPs and ensure reproducibility so that other labs can replicate the work, Khizroev says. Work is underway to meet Good Manufacturing Practices and Good Laboratory Practices manufacturing standards for clinical use.

“While pancreatic cancer is our initial focus,” he says, “we expect the technology to be applicable to many cancers, including glioblastoma. Pancreatic cancer is just the beginning. Once you prove this works in untreatable cancers, everything else follows.”

Moving Toward Precision
Both theranostics and MENPs reflect a broader movement in oncology: pairing highly specific imaging with equally precise treatment. More research, particularly human clinical trials, will be needed before either strategy becomes part of standard care.

“But any tumor with an identifiable, targetable molecular marker is a candidate,” Khizroev says. “That’s the future we’re moving toward: precision imaging paired with precision therapy.”

Khizroev says the work is not an incremental improvement. “This is a new category of cancer treatment.” He is highly confident that even if Cellular Nanomed’s approach is not commercialized first, “this is the direction cancer therapy will move.”

— Beth W. Orenstein of Northampton, Pennsylvania, is a freelance medical writer and regular contributor to Radiology Today.