Site-specific99mTc-labeling of antibody using dihydrazinophthalazine (DHZ) conjugation to Fc region of heavy chain View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2004-09

AUTHORS

Jae Min Jeong, Jaetae Lee, Chang Hum Paik, Dae-Kee Kim, Dong Soo Lee, June-Key Chung, Myung Chul Lee

ABSTRACT

The development of an antibody labeling method with99mTc is important for cancer imaging. Most bifunctional chelate methods for99mTc labeling of antibody incorporate a99mTc chelator through a linkage to lysine residue. In the present study, a novel site-specific99mTc labeling method at carbohydrate side chain in the Fc region of 2 antibodies (T101 and rabbit antihuman serum albumin antibody (RPAb)) using dihydrazinophthalazine (DHZ) which has 2 hydrazino groups was developed. The antibodies were oxidized with sodium periodate to produce aldehyde on the Fc region. Then, one hydrazine group of DHZ was conjugated with an aldehyde group of antibody through the formation of a hydrazone. The other hydrazine group was used for labeling with99mTc. The number of conjugated DHZ was 1.7 per antibody.99mTc labeling efficiency was 46~85% for T101 and 67~87% for RPAb. Indirect labeling with DHZ conjugated antibodies showed higher stability than direct labeling with reduced antibodies. High immunoreactivities were conserved for both indirectly and directly labeled antibodies. A biodistribution study found high blood activity related to directly labeled T101 at early time point as well as low liver activity due to indirectly labeled T101 at later time point. However, these findings do not affect practical use. No significantly different biodistribution was observed in the other organs. The research concluded that DHZ can be used as a site-specific bifunctional chelating agent for labeling antibody with99mTc. Moreover,99mTc labeled antibody via DHZ was found to have excellent chemical and biological properties for nuclear medicine imaging. More... »

PAGES

961-967

Journal

TITLE

Archives of Pharmacal Research

ISSUE

9

VOLUME

27

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf02975851

DOI

http://dx.doi.org/10.1007/bf02975851

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1038220626

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15473668


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