[177Lu]Lu-AKIR001 for CD44v6-Positive Pancreatic Cancer: Preclinical Efficacy and Combination Strategies.

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, with a 5-y survival rate of less than 5% for patients with advanced disease. CD44v6 is frequently overexpressed in the malignancy, representing a promising therapeutic target. Here, we evaluated the efficacy of [177Lu]Lu-AKIR001, a CD44v6-targeting radiopharmaceutical, alone and combined with chemotherapy for the treatment of PDAC. Methods: CD44v6 expression, radioligand binding, and chemotherapy sensitivity were assessed in PDAC cell lines. Mice bearing PDAC xenografts received [177Lu]Lu-AKIR001, chemotherapy, or a combination of the two modalities. Toxicity was determined by body weight monitoring and hematologic and organ analyses. Results: Three of the 4 cell lines expressed CD44v6. In vivo, tumor uptake exceeded 100 %IA/g. Tumor growth inhibition was activity-dependent, with complete remissions detected after the administration of 12 MBq of [177Lu]Lu-AKIR001 (40%) and 4 MBq of [177Lu]Lu-AKIR001 combined with paclitaxel (14%). Conclusion: [177Lu]Lu-AKIR001 demonstrated activity-dependent therapeutic potential in mice bearing PDAC xenografts. Combination therapy with paclitaxel indicated potential synergistic benefit, but further investigation and optimization are warranted.