Intrathoracic 90 Y-NZ-16 therapy improves efficacy and reduces toxicity in pleural mesothelioma mice.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of intrathoracic administration of 90 Y-labeled anti-podoplanin antibody NZ-16 in a pleural mesothelioma murine model, in comparison with conventional intravenous administration. MATERIALS AND METHODS: An intrathoracic mesothelioma model was established using H226-Luc cells in nude mice. Biodistribution and dosimetry were assessed using 111 In-labeled NZ-16. Mice received either intravenous or intrathoracic administration of 90 Y-labeled NZ-16 (3.7 or 7.4 MBq). Tumor growth, survival duration, hematologic toxicity, and histological changes were evaluated. RESULTS: Intrathoracic administration resulted in 1.3-fold higher tumor uptake and reduced accumulation in normal organs compared with intravenous administration. Dosimetric analysis showed lower absorbed doses in bone marrow and lungs with intrathoracic delivery. At 3.7 MBq, intrathoracic administration significantly improved tumor regression and survival compared with the intravenous route. Histological analysis revealed enhanced fibrosis in intrathoracic-treated tumors. Hematologic toxicity was milder with intrathoracic administration. CONCLUSION: Intrathoracic administration of 90 Y-labeled NZ-16 may offer improved therapeutic efficacy and reduced systemic toxicity compared with intravenous administration in pleural mesothelioma. These findings suggest that intrathoracic delivery could be a promising approach for enhancing treatment outcomes in patients with unresectable disease.