RT Journal Article
SR Electronic
T1 Intraperitoneal α-Particle Radioimmunotherapy of Ovarian Cancer Patients: Pharmacokinetics and Dosimetry of <sup>211</sup>At-MX35 F(ab′)<sub>2</sub>—A Phase I Study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1153
OP 1160
DO 10.2967/jnumed.109.062604
VO 50
IS 7
A1 Håkan Andersson
A1 Elin Cederkrantz
A1 Tom Bäck
A1 Chaitanya Divgi
A1 Jörgen Elgqvist
A1 Jakob Himmelman
A1 György Horvath
A1 Lars Jacobsson
A1 Holger Jensen
A1 Sture Lindegren
A1 Stig Palm
A1 Ragnar Hultborn
YR 2009
UL http://jnm.snmjournals.org/content/50/7/1153.abstract
AB 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.