186Re radioimmunotherapy of small cell lung carcinoma xenografts in nude mice.
A 186Re-labeled monoclonal antibody (MAb), NR-LU-10, was used for the radioimmunotherapy of a subcutaneous human small cell lung carcinoma xenograft, SHT-1, in nude mice. Biodistribution with specific and irrelevant labeled MAb demonstrated peak tumor uptake of 8% and 3% of the injected dose/g at 2 days, respectively. Dosimetry analysis predicted tumor:whole-body radiation-absorbed dose ratios of 2.43:1 for NR-LU-10 and 0.62:1 for irrelevant MAb. Single-dose toxicity screening estimated a 50% lethal dose within 30 days of 600 microCi (880 cGy of whole-body radiation). As anticipated, a multiple-dose regimen of 490 microCi in four doses over 10 days (720 cGy of whole-body radiation, eight of eight surviving greater than 30 days) was less toxic than a single bolus dose of 430 microCi (644 cGy of whole-body radiation), six of eight surviving greater than 30 days). A multidose radioimmunotherapy regimen was initiated in nude mice bearing 66-mm3 tumors (total dose, 500 to 600 microCi). Complete remissions (greater than 140 days) were achieved in three of 16 mice, and the remainder showed a mean tumor growth delay of 53 days. Matched doses with irrelevant MAb produced one remission, one treatment-related death, and a mean growth delay of only 20 days in six of eight mice. Thus, in this nonoptimal radioimmunotherapy model, significant antitumor responses were observed using a mildly toxic multiple dosing regimen.
Beaumier
P L
PL
NeoRx Corporation, Seattle, Washington 98119.
Venkatesan
P
P
Vanderheyden
J L
JL
Burgua
W D
WD
Kunz
L L
LL
Fritzberg
A R
AR
Abrams
P G
PG
Morgan
A C
AC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001345:Autoradiography; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002460:Cell Line; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium