Preparation of Ga-67 labeled monoclonal antibodies using deferoxamine as a bifunctional chelating agent
Ga-67 labeled monoclonal IgG or F(ab')/sub 2/ fragments against ..cap alpha..-fetoprotein and ..beta..-subunit of human choriogonadotropin (HCG), were prepared using Deferoxamine (DFO) as a bifunctional chelating agent. DFO, a well-known iron chelating agent, was conjugated with monoclonal antibodies (Ab) by a glutaraldehyde two step method and the effect of conjugation on the Ab activities was examined by RIA and Scatchard plot analysis. In both monoclonal Ab preparations, the conjugation reaction was favored as the pH increased. However, Ab-binding activities decreased as the molecular ratios of DFO to Ab increased. Preserved Ab activities were observed when Ab contained DFO per Ab molecule less than 2.1. At a ratio of over 3.3 DFO molecules per Ab, the maximal binding capacity rather than the affinity constant decreased. The inter-molecular cross linkage seemed to be responsible for the deactivation of binding activities. The obtained DFO-Ab conjugates, were then easily labeled with high efficiency and reproducibility and Ga-67 DFO-Ab complexes were highly stable both in vitro and in vivo. Thus, biodistribution of Ga-67 labeled F(ab')/sub 2/ fragments of monoclonal Ab to HCG ..beta..-subunit was attempted in nude mice transplanted with HCG-producing human teratocarcinoma. Tumor could be visualized, in spite of relatively high background imaging of liver, kidney and spleen. The use of DFO as a bifunctional chelating agent provided good evidence for its applicability to labeling monoclonal Ab with almost full retention of Ab activities. Further, availability of Ga-68 will make Ga-68 DFO-monoclonal Ab a very useful tool for positron tomography imaging of various tumors.
- Research Organization:
- Kyoto Univ., Kyoto
- OSTI ID:
- 6780855
- Report Number(s):
- CONF-840619-
- Journal Information:
- J. Nucl. Med.; (United States), Journal Name: J. Nucl. Med.; (United States) Vol. 25:5; ISSN JNMEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550602 -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AFFINITY
ALDEHYDES
AMINES
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BINDING ENERGY
CHELATING AGENTS
CHEMICAL PREPARATION
COMPUTERIZED TOMOGRAPHY
DAYS LIVING RADIOISOTOPES
DEACTIVATION
DEFEROXAMINE
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DIAGNOSTIC USES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
ENERGY
GALLIUM 67
GALLIUM 68
GALLIUM ISOTOPES
HOURS LIVING RADIOISOTOPES
IMAGE PROCESSING
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLING
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PH VALUE
POSITRON COMPUTED TOMOGRAPHY
PROCESSING
QUANTITY RATIO
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
RADIOISOTOPES
SYNTHESIS
TOMOGRAPHY
TRACER TECHNIQUES
USES