186Re radioimmunotherapy of small cell lung carcinoma xenografts in nude mice

Journal Article · Tue Jan 15 04:00:00 EST 1991 · Cancer Research; (USA)

OSTI ID:6210217

Beaumier, P L; Venkatesan, P; Vanderheyden, J L; Burgua, W D; Kunz, L L; Fritzberg, A R; Abrams, P G; Morgan, Jr, A C ^[1]

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1. NeoRx Corporation, Seattle, WA (USA)

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.

• OSTI ID: 6210217
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 51:2; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARCINOMAS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSES
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
HEAVY NUCLEI
IMMUNOLOGY
IMMUNOTHERAPY
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LUNGS
MAMMALS
MEDICINE
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANS
RADIATION DOSES
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RESPIRATORY SYSTEM
RHENIUM 186
RHENIUM ISOTOPES
RODENTS
THERAPY
VERTEBRATES