Preparation and in vivo evaluation of an N-(p-[125I]iodophenethyl)maleimide-antibody conjugate

Preparation and in vivo evaluation of an N-(p-[125I]iodophenethyl)maleimide-antibody conjugate

Protein sulfhydryl reactive N-(4-[125I]iodophenethyl)maleimide (IPEM, 5) was obtained from N-[4-(tri-n-butylstannyl)phenethyl]maleimide in 59-100% radiochemical yield. Conjugation of 5 to NR-ML-05 Fab, a murine anti-melanoma antibody Fab fragment that had been previously reduced with dithiothreitol...

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Bibliographic Details
Published in:Bioconjugate chemistry Vol. 2; no. 6; pp. 435 - 440
Main Authors: Hylarides, Mark D, Wilbur, D. Scott, Reed, Michael W, Hadley, Stephen W, Schroeder, Joan R, Grant, Leah M
Format: Journal Article
Language:English
Published: United States American Chemical Society 01-11-1991
Subjects:
Animals
Antigens, Neoplasm - immunology
Dithiothreitol
Female
Immunoglobulin Fab Fragments
Iodine Radioisotopes
Iodobenzenes - chemical synthesis
Iodobenzenes - chemistry
Iodobenzenes - pharmacokinetics
Isotope Labeling - methods
Maleimides - chemical synthesis
Maleimides - chemistry
Maleimides - pharmacokinetics
Melanoma - immunology
Melanoma, Experimental - metabolism
Mice
Mice, Nude
Stomach - metabolism
Thyroid Gland - metabolism
Tissue Distribution
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Summary:Protein sulfhydryl reactive N-(4-[125I]iodophenethyl)maleimide (IPEM, 5) was obtained from N-[4-(tri-n-butylstannyl)phenethyl]maleimide in 59-100% radiochemical yield. Conjugation of 5 to NR-ML-05 Fab, a murine anti-melanoma antibody Fab fragment that had been previously reduced with dithiothreitol (DTT), was effected in an average of 85% yield. Results from in vitro chemical challenges and serum stability studies on the IPEM conjugate of NR-ML-05 Fab (6) indicated a stable covalent attachment of the radioiodine. A biodistribution study of the IPEM conjugate in tumor-bearing athymic nude mice showed lack of significant accumulation of radioiodine in the thyroid and stomach which was an indication of in vivo stability. The observed uptake in tumor was consistent with that obtained for Chloramine-T- or p-iodobenzoate-labeled NR-ML-05 Fab conjugates.
Bibliography:ark:/67375/TPS-TP6VWND3-R
istex:9BD350E768305708BA0027AA4823C4A2DBA79B2F
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1043-1802
1520-4812
DOI:10.1021/bc00012a010