Intraperitoneal alpha-particle radioimmunotherapy of ovarian cancer patients: pharmacokinetics and dosimetry of (211)At-MX35 F(ab')2--a phase I study
| Autor: | Lars Jacobsson, Jakob Himmelman, Elin Cederkrantz, Stig Palm, Ragnar Hultborn, Tom Bäck, Holger Jensen, Håkan Andersson, Sture Lindegren, Chaitanya R. Divgi, Jörgen Elgqvist, György Horvath |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
medicine.medical_specialty Pathology medicine.medical_treatment Urology Abdominal cavity Pharmacokinetics medicine Humans Radiology Nuclear Medicine and imaging Infusions Parenteral Radiometry Aged Ovarian Neoplasms Chemotherapy business.industry Antibodies Monoclonal Radiotherapy Dosage Middle Aged Radioimmunotherapy medicine.disease Alpha Particles Radiation therapy medicine.anatomical_structure Treatment Outcome Monoclonal Body Burden Female Radiopharmaceuticals business Ovarian cancer Recurrent Ovarian Carcinoma Astatine |
| Zdroj: | Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 50(7) |
| ISSN: | 0161-5505 |
| Popis: | The alpha-emitter (211)At 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.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. (211)At was labeled to MX35 F(ab')(2) using the reagent N-succinimidyl-3-(trimethylstannyl)-benzoate. Patients were infused with (211)At-MX35 F(ab')(2) (22.4-101 MBq/L) in dialysis solution via the peritoneal catheter. gamma-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.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.This study indicates that by intraperitoneal administration of (211)At-MX35 F(ab')(2) it is possible to achieve therapeutic absorbed doses in microscopic tumor clusters without significant toxicity. |
| Databáze: | OpenAIRE |
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