Hyperthermia enhances localization of sup 111 In-labeled hapten to bifunctional antibody in human colon tumor xenografts
- Loma Linda Univ. School of Medicine, CA (USA)
A unique bifunctional antibody (BFA) delivery system was examined for radiolocalization and distribution following hyperthermia (41.5 degrees C, 45 min) of T380h human colon tumor xenografts. The BFA is an F(ab')2 fragment made by combining two murine monoclonal antibodies with different specificities, one directed against carcinoembryonic antigen (monoclonal antibody CEM 231) and the other (monoclonal antibody CHA 255) against a hapten found on a derivative of 111In-labeled benzyl-EDTA (EOTUBE). This BFA is known as CEM/CHA. The CEM/CHA accumulates in carcinoembryonic antigen-expressing tissue and clears from normal tissues prior to administration of the radiolabeled hapten. T380h tumor chunks were injected s.c. into 31 nude mice. Two weeks later mean tumor volume was 352 mm3 and the animals were assigned to one of four groups: (a) CEM/CHA + hyperthermia + 111In-EOTUBE; (b) CHA 255 F(ab')2 + hyperthermia + 111In-EOTUBE, and (c and d) treated in the same manner as a and b, respectively, but without heat. The CEM/CHA, CHA 255 F(ab')2, and 111In-labeled hapten were injected i.p. at 14 micrograms, 7 micrograms, and 140-200 microCi/mouse, respectively. The hyperthermia was administered 22-24 h after BFA and the radiolabeled hapten was injected 2 h later. Twenty-four h thereafter, the animals were euthanized for testing. A significantly greater percentage of injected radioactivity localized within heated compared to unheated tumors in mice given CEM/CHA and 111In-EOTUBE (7.39%/g tumor and 4.46%/tumor versus 2.72%/g tumor and 1.44%/tumor, respectively). The percentage of kidney activity in mice given CHA 255 F(ab')2 fragments and heat was 57% lower than in the nonheated group when expressed on a per g basis (12.73 and 22.20%, respectively). Microautoradiography showed greater radiolocalization in heated tumors than in nonheated control tumors of comparable size.
- OSTI ID:
- 5919906
- Journal Information:
- Cancer Research; (USA), Vol. 51:5; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
Similar Records
Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: Imaging of tumors hosted in nude mice
Pharmacokinetics of /sup 99m/Tc(Sn)- and /sup 131/I-labeled anti-carcinoembryonic antigen monoclonal antibody fragments in nude mice
Related Subjects
HYPERTHERMIA
BIOLOGICAL EFFECTS
LARGE INTESTINE
EXPERIMENTAL NEOPLASMS
MONOCLONAL ANTIBODIES
BIOLOGICAL LOCALIZATION
AUTORADIOGRAPHY
CEA
INDIUM 111
MICE
TISSUE DISTRIBUTION
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BODY
BODY TEMPERATURE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
FRENCH ORGANIZATIONS
GASTROINTESTINAL TRACT
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
INTESTINES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MINUTES LIVING RADIOISOTOPES
NATIONAL ORGANIZATIONS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RODENTS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics