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

Journal of Nuclear Medicine

Jörgen Elgqvist¹  Stig Palm¹  Tom Bäck¹  Chaitanya Divgi¹  Holger Jensen¹  Ragnar Hultborn¹  Håkan Andersson¹  Jakob Himmelman¹  Elin Cederkrantz¹  György Horvath¹  Sture Lindegren¹  Lars Jacobsson¹ 

关键词: astatine;    dosimetry;    pharmacokinetics;    radioimmunotherapy;    clinical study;   

DOI  :  10.2967/jnumed.109.062604

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The α-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. γ-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.

【 授权许可】

Unknown