111In-표지 갈락토즈 접합 항체의 체내분포 및 간에서의 대사:111In-표지 항체와의 비교연구 (Biodistribution and Hepatic Metabolism of Galactosylated 111In-Antibody-Chelator Conjugates: Comparison with 111In-Antibody-Chelator Conjugates) |
Author |
곽동석,이재태,정규식,하정희,안병철,이규보,백창흠, |
Dong Suk Kwak, MD, Jaetae Lee, MD, Kyu Sik Jeong, PhD, Jeoung Hee Ha, MD,Byeong Cheol Ahn, MD, Kyubo Lee, MD, Chang H. Paik PhD |
Affiliation |
경북대학교 의과대학 핵의학교실, 수의과대학 수의학과, 영남대학교 의과대학 약리학교실, 미국국립보건원 임상센터 핵의학과 Department of Nuclear Medicine, Medical School, Department of Veterinary Medicine1, Veterinary College,Kyungpook National University, Department of Pharmacology, Yeoungnam University Medical School, Daegu,Korea, and Department of Nuclear Medicine, Clinica |
Abstract |
Purpose : To evaluate the use of monoclonal antibody
(MoAb) as a carrier of the receptor-binding ligand,
the receptor mediated uptake into liver and subsequent
metabolism of 111In-labeled galactosylated
MoAb-chelator conjugates were investigated and compared
with those of 111In labeled MoAb. Materials
and Methods : T101 MoAb, IgG2 against human lymphocytic
leukemic cell, conjugated with cyclic DTPA
dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-
methyl-DTPA (1B4M) was galactosylated with
2-imino-2-methoxyethyl-1-thio-β-D-galactose and then
radiolabeled with 111In. Biodistribution and
metabolism study was performed with two 111In-
conjugates in mice and rats. Results : 111In-labeled
T101
and its galactosylated conjugates were taken to the
liver by the time, mostly within 10 min. However DTPA
conjugate was retained longer in the liver than the
1B4M conjugate (55% vs 20% of injected dose at 44
hr). During this time, the radiometabolite of DTPA
conjugate was excreted similarly into urine (24%) and
feces (17%). The radiometabolite of 1B4M was excreted
primarily into feces (68%) rather than urine (8%).
Size exclusion HPLC analysis of the bile and
supernatant of liver homogenate showed two peaks, the
first
(35%) with the retention time (Rt) identical to IgG and
the second (65%) with Rt similar to free 111In at 3
hr post-injection for the 1B4M conjugate, indicating
that the metabolite is rapidly excreted through the
biliary
system. In contrast to DTPA conjugate, the small 111In-
DTPA-like metabolite was the major radioindium
component (90%) in the liver homogenate as early as 3
hour post-injection, but the cumulative radioindium
activity in feces was only 17% at 44 hour, indicating
that the metabolite from DTPA conjugate does not clear
readily through the biliary tract. Conclusion : The
galactosylation of the MoAb conjugates resulted in
higher
hepatocyte uptake and enhanced metabolism, compared to
those without galactosylation. Metabolism of the
MoAb-conjugates is different between compounds
radiolabled with different chelators due to different
characteristics of radiometabolites generated in the
liver. |
Keyword |
Biodistribution, Metabolism, Galactosylated antibody, 111In-labeled antibody |
Full text Article |
3706402.pdf
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