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Intraperitoneal -Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of ²¹¹At-MX35 F(ab')₂—A Phase I Study

¹ Department of Oncology, University of Gothenburg, Gothenburg, Sweden; ² Department of Radiation Physics, University of Gothenburg, Gothenburg, Sweden; ³ Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; and ⁴ PET and Cyclotron Unit, Rigshospitalet, Copenhagen, Denmark

Correspondence: For correspondence or reprints contact: Ragnar Hultborn, Department of Oncology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. E-mail: ragnar.hultborn{at}oncology.gu.se

The -emitter ²¹¹At labeled to a monoclonal antibody has proven safe and effective in treating microscopic ovarian cancer in the abdominal cavity of mice. Women in complete clinical remission after second-line chemotherapy for recurrent ovarian carcinoma were enrolled in a phase I study. The aim was to determine the pharmacokinetics for assessing absorbed dose to normal tissues and investigating toxicity. Methods: Nine patients underwent laparoscopy 2–5 d before the therapy; a peritoneal catheter was inserted, and the abdominal cavity was inspected to exclude the presence of macroscopic tumor growth or major adhesions. ²¹¹At was labeled to MX35 F(ab')₂ using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with ²¹¹At-MX35 F(ab')₂ (22.4–101 MBq/L) in dialysis solution via the peritoneal catheter. -camera scans were acquired on 3–5 occasions after infusion, and a SPECT scan was acquired at 6 h. Samples of blood, urine, and peritoneal fluid were collected at 1–48 h. Hematology and renal and thyroid function were followed for a median of 23 mo. Results: Pharmacokinetics and dosimetric results were related to the initial activity concentration (IC) of the infused solution. The decay-corrected activity concentration decreased with time in the peritoneal fluid to 50% IC at 24 h, increased in serum to 6% IC at 45 h, and increased in the thyroid to 127% ± 63% IC at 20 h without blocking and less than 20% IC with blocking. No other organ uptakes could be detected. The cumulative urinary excretion was 40 kBq/(MBq/L) at 24 h. The estimated absorbed dose to the peritoneum was 15.6 ± 1.0 mGy/(MBq/L), to red bone marrow it was 0.14 ± 0.04 mGy/(MBq/L), to the urinary bladder wall it was 0.77 ± 0.19 mGy/(MBq/L), to the unblocked thyroid it was 24.7 ± 11.1 mGy/(MBq/L), and to the blocked thyroid it was 1.4 ± 1.6 mGy/(MBq/L) (mean ± SD). No adverse effects were observed either subjectively or in laboratory parameters. Conclusion: This study indicates that by intraperitoneal administration of ²¹¹At-MX35 F(ab')₂ it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity.

Key Words: astatine • dosimetry • pharmacokinetics • radioimmunotherapy • clinical study

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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