Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-88 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity

Journal Article · Mon May 15 00:00:00 EDT 1989 · Cancer Research; (USA)

OSTI ID:5561569

Kozak, R W; Raubitschek, A; Mirzadeh, S; Brechbiel, M W; Junghaus, R; Gansow, O A; Waldmann, T A ^[1]

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1. Center for Biologics Evaluation and Research, FDA, Bethesda, MD (USA)

One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B.

• OSTI ID: 5561569
• Journal Information: Cancer Research; (USA), Vol. 49:10; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
CHELATING AGENTS
STABILITY
LYMPHOKINES
RECEPTORS
MONOCLONAL ANTIBODIES
SPECIFICITY
RADIOIMMUNOTHERAPY
EFFICIENCY
EXPERIMENTAL NEOPLASMS
IN VIVO
IODINE 131
MICE
TISSUE DISTRIBUTION
YTTRIUM 88
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MAMMALS
MEDICINE
MEMBRANE PROTEINS
MITOGENS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOIMMUNOLOGY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RODENTS
SECONDS LIVING RADIOISOTOPES
THERAPY
VERTEBRATES
YTTRIUM ISOTOPES
550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)