In vivo tumor localization of technetium-labeled metalothionein/monoclonal antibody conjugates
The use of radioiodinated monoclonal antibodies (MAb) directed against tumor associated antigens for imaging has reinforced the need for additional labeling methods to permit the use of other medically relevant radionuclides. The low molecular weight metal binding protein, metallothionein (MT) has a high avidity for several radionuclides including Tc-99m. The conjugation of a Zn-MT to MAb B6.2 directed against human breast carcinoma was studied using glutaraldehyde as the bifunctional cross-linker. The Zn-MT-B6.2 conjugate was labeled with Tc-99m to form a Tc-99m labeled MT-B6.2 conjugate. Radiolabeled conjugates were shown to retain high immunoreactivity compared to radio-iodinated B6.2 in a direct cell binding assay on target MCF7 breast carcinoma cells and a low non-specific binding to antigen negative melanoma cells. These conjugates were evaluated in athymic mice bearing subcutaneous Clouser breast or A375 nonspecific melanoma tumors. The specificity of uptake in the target tumor to nonspecific tumor was equivalent to that of the radioiodinated antibody over the first 24 hours in vivo. The blood clearance was more rapid for the Tc-99m MT conjugates and this enhanced clearance permitted superior images to be obtained within 24 hours. This labeling methodology produces stable Tc-99m labeled antibodies, retaining high immunoreactivity and demonstrating good localization and imaging in this model system.
- Research Organization:
- New England Nuclear Corp., Immunopharmaceutical R and D Dept., No. Billerica, MA 01862
- OSTI ID:
- 6594233
- Report Number(s):
- CONF-840619-; TRN: 87-018886
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 25:5; Conference: 31. annual meeting of the Society of Nuclear Medicine, Los Angeles, CA, USA, 5 Jun 1984
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
MONOCLONAL ANTIBODIES
LABELLING
NEOPLASMS
SCINTISCANNING
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
ANTIGENS
CARCINOMAS
IN VIVO
MAMMARY GLANDS
MELANOMAS
METALLOTHIONEIN
PROTEINS
RADIOIMMUNOLOGY
RADIONUCLIDE KINETICS
RETENTION FUNCTIONS
TECHNETIUM 99
TISSUE DISTRIBUTION
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
DRUGS
FUNCTIONS
GLANDS
HOURS LIVING RADIOISOTOPES
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
METALLOPROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
RADIOISOTOPE SCANNING
RADIOISOTOPES
SYNTHESIS
TECHNETIUM ISOTOPES
YEARS LIVING RADIOISOTOPES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
400702 - Radiochemistry & Nuclear Chemistry- Properties of Radioactive Materials