Optimization of an antibreast carcinoma monoclonal antibody as a tumor imaging agent

Conference · Sun Jan 01 04:00:00 EST 1984 · J. Nucl. Med.; (United States)

OSTI ID:6844199

Zalutsky, M R; Colcher, D; Kaplan, W D; Schlom, J; Kufe, D

The authors have previously reported that monoclonal antibody B6.2 and its fragments labeled with I-125 selectively localizes in human breast tumor (bt) xeongrafts in nude mice. Herein the authors compare I-125 B6.2 and its fragments with regard to (a) in vitro binding to bt extracts and (b) blood clearance. Antibody B6.2 and fragments were labeled using iodogen and then incubated with cell extracts of a human bt metastasis to the liver (Met.173), MCF-7 bt line, and normal human liver. Scatchard analysis of the data revealed that I-125-B6.2 and its fragments bound to both breast tumors with affinity constants of the order of 10/sup 9/M/sup -1/; no specific binding to normal liver was observed. The affinity constant for both divalent fragments was higher than that observed for the monovalent Fab' fragment. Serial sampling of blood from tumor bearing mice indicated that the blood clearance of F(ab')/sub 2/ was more rapid than IgG and that Fab' cleared considerably faster still. A comparison of the biodistribution at 0.1 and 5 ..mu..g protein per mouse suggests that with 1 gm tumors, lower doses do not necessarily result in better tumor-to-tissue ratios. When the blood clearance of I-125-B6.2 was compared to that of a non-specific IgG (MOPC), a much faster clearance of I-125 activity, significantly greater than that resultant from uptake in the tumor, was observed. Accelerated blood clearance may be due to selective catabolism of the specific antibody. When I-125 labeled B6.2 was injected into mice bearing breast and melanoma tumors, the thyroid uptake of I-125 activity was 2-3 times greater in the bt mice. The authors conclude that catabolism may be an important factor in determining the optimal radiolabel for immunoscintigraphy.

• Research Organization: Harvard Medical School, Boston, MA
• OSTI ID: 6844199
• Report Number(s): CONF-840619-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 25:5
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AFFINITY
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BIOLOGICAL MATERIALS
BLOOD
BODY
BODY FLUIDS
CARCINOMAS
CLEARANCE
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
GRAFTS
IMAGE PROCESSING
IN VITRO
INCUBATION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLING
LIVER
MAMMALS
MAMMARY GLANDS
MATERIALS
MELANOMAS
METASTASES
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
OPTIMIZATION
ORGANS
PROCESSING
RADIOISOTOPE SCANNING
RADIOISOTOPES
RODENTS
SCINTISCANNING
TRANSPLANTS
USES
VERTEBRATES