Abstract
The prognosis of advanced mesothelioma is poor. Podoplanin (PDPN) is highly expressed in most malignant mesothelioma. This study aimed to evaluate the potential alpha-radioimmunotherapy (RIT) with a newly developed anti-PDPN antibody, NZ-16, compared with a previous antibody, NZ-12. Methods: The in vitro properties of radiolabeled antibodies were evaluated by cell binding and competitive inhibition assays using PDPN-expressing H226 mesothelioma cells. The biodistribution of 111In-labeled antibodies was studied in tumor-bearing mice. The absorbed doses were estimated based on biodistribution data. Tumor volumes and body weights of mice treated with 90Y- and 225Ac-labeled NZ-16 were measured for 56 days. Histologic analysis was conducted. Results: The radiolabeled NZ-16 specifically bound to H226 cells with higher affinity than NZ-12. The biodistribution studies showed higher tumor uptake of radiolabeled NZ-16 compared with NZ-12, providing higher absorbed doses to tumors. RIT with 225Ac- and 90Y-labeled NZ-16 had a significantly higher antitumor effect than RIT with 90Y-labeled NZ-12. 225Ac-labeled NZ-16 induced a larger amount of necrotic change and showed a tendency to suppress tumor volumes and prolonged survival than 90Y-labeled NZ-16. There is no obvious adverse effect. Conclusions: Alpha-RIT with the newly developed NZ-16 is a promising therapeutic option for malignant mesothelioma.
Highlights
A strong intensity was observed on the cell membranes of H226 (Figure S1)
These results indicate that the DOTA conjugation procedure that of NZ-12
Our finding indicates that the relative biologic effect (RBE) of 225 Ac-labeled NZ-16 is 5.7, which is similar to the recommended amount for α-emitters by the Medical Internal
Summary
Malignant mesothelioma is an aggressive tumor that arises primarily in the pleural or peritoneal mesothelial surfaces [1]. Surgical resection is only offered to patients with early-stage disease [1,2]. Most patients reach advanced-stage disease before diagnosis, and the primary treatment is systemic chemotherapy [1,2]. The prognosis is poor and the median overall survival of patients who undergo chemotherapy is approximately
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