Iodination of Fab fragments: Effect of I/Fab molar ratio
Radioisotopes of iodine covalently coupled to antibodies have formed the standard against which other radiolabeled antibody tracers are compared. Since the use of monoclonal antibodies (MoAb) for the diagnosis and therapy of malignant diseases is increasing rapidly the authors wished to investigate radiolabeling variables which affect the immunointegrity of radioiodinated antibodies. The authors studied the electrophilic (chloramine-T) iodination of the Fab fragment of a murine MoAb against the high molecular weight proteoglycan antigen of human melanoma. The immunoreactivity of the iodianted Fab was assessed using a cell binding assay with formaldehyde-fixed cells of a selected cell line (number 2669). The in vitro stability of the labeled fragment was studied electrophoretically. The results indicate that the reaction time and concentrations of chloramine-T were not critical within broad limits. On the other hand immunoreactivity and deiodination over time (shelf-life) were inversely related and very sensitive to I/Fab molar ratio even at concentrations below -0.1 atom of I per Fab molecule. This has important implications for the radiotherapy of malignant tumors using I-131 labeled immunoglobulins which often have higher I/Fab molar ratios (100 mCi I-131/10 mg Fab approx. = 0.5 I atoms/Fab) versus diagnostic preparations (10 mCi I-131/5 mg Fab approx. = 0.1 I atoms/Fab). Thus the authors conclude that to maintain high immunointegrity the I/Fab molar ratio should be kept low, especially for therapeutic preparations, by using correspondingly higher amounts of Fab.
- Research Organization:
- Univ. of Washington and Oncogen, Seattle, WA
- OSTI ID:
- 6791814
- Report Number(s):
- CONF-850611-; TRN: 87-011055
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CHLORAMINES
CHEMICAL REACTION KINETICS
MONOCLONAL ANTIBODIES
LABELLING
NEOPLASMS
RADIOIMMUNOTHERAPY
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
CHEMICAL REACTION YIELD
EFFICIENCY
IODINE ISOTOPES
METABOLITES
MUCOPOLYSACCHARIDES
AMINES
ANTIBODIES
CARBOHYDRATES
DISEASES
DRUGS
IMMUNOLOGY
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MEDICINE
NUCLEAR MEDICINE
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
POLYSACCHARIDES
RADIOIMMUNOLOGY
RADIOLOGY
RADIOTHERAPY
REACTION KINETICS
SACCHARIDES
SYNTHESIS
THERAPY
YIELDS
550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)
550601 - Medicine- Unsealed Radionuclides in Diagnostics