Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials.
Rhenium is a radionuclide with physical and chemical properties suitable for radioimmunotherapy. Two Phase I trials were carried out using 186Re-labeled murine monoclonal antibodies. Patients with refractory metastatic epithelial carcinoma received single doses of either 186Re-labeled intact NR-LU-10, a pancarcinoma antibody, 25-120 mCi/m2 (n = 15) or 186Re-labeled F(ab')2 fragment of NR-CO-02, an anti-CEA variant antibody, 25-200 mCi/m2 (n = 31). Prior to radioimmunotherapy, tumor localization of antibody was confirmed by 99mTc-labeled NR-LU-10 Fab or 99mTc-labeled NR-CO-02 F(ab')2 imaging. Dose-limiting myelosuppression was observed at 120 mCi/m2 following 186Re-NR-LU-10 intact antibody and at 150 mCi/m2 following NR-CO-02 F(ab')2 fragment in heavily pretreated patients. In patients with minimal prior therapy, a maximum tolerated dose for NR-CO-02 F(ab')2 was not reached by 200 mCi/m2. Non-marrow toxicity was minimal. Human anti-mouse antibody developed in all patients receiving intact NR-LU-10, and in 86% patients receiving F(ab')2 NR-CO-02. One patient treated with 186Re NR-CO-02 achieved a partial response. We conclude that 186Re-labeled antibody can be safely administered with significant toxicity limited to marrow.
Breitz
H B
HB
Department of Radiology, Virginia Mason Medical Center, Seattle, Washington 98111.
Weiden
P L
PL
Vanderheyden
J L
JL
Appelbaum
J W
JW
Bjorn
M J
MJ
Fer
M F
MF
Wolf
S B
SB
Ratliff
B A
BA
Seiler
C A
CA
Foisie
D C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium