Biodistribution, pharmacokinetic, and imaging studies with sup 186 Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice

Journal Article · Sat Dec 15 04:00:00 EST 1990 · Cancer Research; (USA)

OSTI ID:6070146

Goldrosen, M H; Biddle, W C; Pancook, J; Bakshi, S; Vanderheyden, J L; Fritzberg, A R; Morgan, Jr, A C; Foon, K A ^[1]

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1. Roswell Park Cancer Institute, Buffalo, NY (USA)

Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re-labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained.

• OSTI ID: 6070146
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:24; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BODY
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GLANDS
HEAVY NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIVER
MAMMALS
METASTASES
MICE
MONOCLONAL ANTIBODIES
NUCLEI
ODD-ODD NUCLEI
ORGANS
RADIOIMMUNODETECTION
RADIOIMMUNOSCINTIGRAPHY
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOPHARMACEUTICALS
RHENIUM 186
RHENIUM ISOTOPES
RODENTS
SCINTISCANNING
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES