Comparison of the pharmacokinetics of I-125 and In-111 labeled intact and proteolytic fragments of a monoclonal antibody

Conference · Wed May 01 04:00:00 EDT 1985 · J. Nucl. Med.; (United States)

OSTI ID:7028835

Brown, B A; Comeau, R D; Jones, P L; Liberatore, F A; Neacy, W P; Sands, H; Gallagher, B M

Intact I-125-B72.3 has been previously shown to selectively localize in the LS174T (human colon carcinoma) xenografts in athymic mice. The purpose of these studies was to compare the pharmacokinetics of In-111 and I-125 labeled intact B72.3 F(ab')/sub 2/, and Fab in this model. B72.3 Fab was prepared by standard methods while the F(ab')/sub 2/ required a modified papain digestion protocol. B72.3 was either radioiodinated or labeled with In-111 after dianhydride DTPA modification. These procedures did not significantly alter the immunoreactivity toward the target cell line. Intact B72.3 labeled with either isotope imaged LS174T and the biodistribution of both labeled antibodies were similar in all organs except liver. LS174T uptake was 40% I.D./gram for In-111-B72.3 and 30% I.D./gram for I-125-B72.3. In-111-B72.3 liver uptake was 20% I.D./g while that of I-125-B72.3 was 4% I./D./g. Both I-125 and In-111 labeled F(ab')/sub 2/ of B72.3 imaged the LS174T tumor. In contrast, the Fab labeled with either isotope did not produce specific images. The blood clearance was Fab>F(ab')/sub 2/> intact B72.3 for both isotopes. The In-111-B72.3 Fab and F(ab')/sub 2/ accumulated in the kidneys and persisted for days. With either isotope, intact B72.3 gave similar tumor to tissue ratios while I-125-F(ab')/sub 2/ was superior to In-111-F9ab')/sub 2/. This was not due to an increased uptake of radioiodinated fragments (approx. =In-111) but to a more rapid clearance from the background. The more rapid clearance of activity observed with radioiodinated fragments may be advantageous for certain applications. The different patterns of distribution for the various forms of B72.3 with different isotopes suggest that the most desirable combination of antibody form and label will depend on the intended use.

• Research Organization: Immunopharmaceutical R and D, E.I. duPont de Nemours, North Billerica, MA 01862
• OSTI ID: 7028835
• Report Number(s): CONF-850611-
• Conference Information: Journal Name: J. Nucl. Med.; (United States) Journal Volume: 26:5
• Country of Publication: United States
• Language: English

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550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
CARBOXYLIC ACIDS
CARCINOEMBRYONIC ANTIGEN
CHELATING AGENTS
CHEMICAL PREPARATION
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
DRUGS
DTPA
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
FUNCTIONS
IMMUNOLOGY
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LABELLING
MEDICINE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDES
PROTEINS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIONUCLIDE KINETICS
RADIOPHARMACEUTICALS
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
REACTION KINETICS
RETENTION FUNCTIONS
SYNTHESIS
THERAPY
TISSUE DISTRIBUTION
UPTAKE