HMN 2026: How New targeted radiopharmaceutical therapy induces remission in pancreatic cancer model

A newly developed targeted radiopharmaceutical treatment can effectively slow tumor growth in pancreatic ductal adenocarcinoma (PDAC), according to new research published in the May issue of The Journal of Nuclear Medicine. In preclinical models, the treatment achieved complete remission of the disease, highlighting its potential to transform care for this highly aggressive cancer.

PDAC accounts for more than 90% of pancreatic cancer cases and remains one of the most lethal malignancies, with a five-year survival rate of less than 5% in patients with metastatic disease. Although surgery is the only curative approach, it is feasible only in 10%–20% of patients with localized disease.

“PDAC is very difficult to treat, and new options are urgently needed,” said Marika Nestor, professor in the Department of Immunology, Genetics and Pathology at Uppsala University in Sweden. “Our previous findings suggest a possible new targeted treatment approach for pancreatic cancer patients whose tumors express CD44v6, which may help make treatment more precise and effective.”

In the study, researchers evaluated the CD44v6-targeted radiopharmaceutical ¹⁷⁷Lu-AKIR001 as a treatment on its own, as well as paired with standard chemotherapy. CD44v6 expression, radioligand binding, and chemotherapy sensitivity were first assessed in four PDAC cell lines. Next, mice bearing PDAC xenografts received ¹⁷⁷Lu-AKIR001, chemotherapy, or a combination of the two modalities. Therapeutic efficacy and toxicity for each treatment approach were then determined.

Three of the four PDAC cell lines were found to express CD44v6. In the mouse studies, tumor uptake of ¹⁷⁷Lu-AKIR001 was very strong and selective. Tumor growth inhibition was activity-dependent, with complete remissions detected after the administration of 12 MBq of ¹⁷⁷Lu-AKIR001 (40%) and four MBq of ¹⁷⁷Lu-AKIR001 combined with paclitaxel chemotherapy (14%). No significant toxicity was observed.

“Targeted radiotherapies have already transformed treatment for prostate and neuroendocrine tumors,” said Nestor. “Our findings suggest that CD44v6 can be added to the list of targets that can be reached with this approach, and, importantly, in a cancer where we desperately need new options.”

¹⁷⁷Lu-AKIR001 radiopharmaceutical therapy is currently being evaluated in patients with other malignancies. The clinical program has recently been expanded to allow broader patient inclusion, and this work can help guide how it could be used in the future, according to Nestor.

Provided by
Society of Nuclear Medicine and Molecular Imaging

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