Development of 124I immuno-PET targeting tumor vascular TEM1/endosialin.

Details

Serval ID
serval:BIB_38FBECAB0189
Type
Article: article from journal or magazin.
Collection
Publications
Title
Development of 124I immuno-PET targeting tumor vascular TEM1/endosialin.
Journal
Journal of Nuclear Medicine
Author(s)
Chacko A.M., Li C., Nayak M., Mikitsh J.L., Hu J., Hou C., Grasso L., Nicolaides N.C., Muzykantov V.R., Divgi C.R., Coukos G.
ISSN
1535-5667 (Electronic)
ISSN-L
0161-5505
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
55
Number
3
Pages
500-507
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Tumor endothelial marker 1 (TEM1/endosialin) is a tumor vascular marker highly overexpressed in multiple human cancers with minimal expression in normal adult tissue. In this study, we report the preparation and evaluation of (124)I-MORAb-004, a humanized monoclonal antibody targeting an extracellular epitope of human TEM1 (hTEM1), for its ability to specifically and sensitively detect vascular cells expressing hTEM1 in vivo.
METHODS: MORAb-004 was directly iodinated with (125)I and (124)I, and in vitro binding and internalization parameters were characterized. The in vivo behavior of radioiodinated MORAb-004 was characterized in mice bearing subcutaneous ID8 tumors enriched with mouse endothelial cells expressing hTEM1 and by biodistribution and small-animal immuno-PET studies.
RESULTS: MORAb-004 was radiolabeled with high efficiency and isolated in high purity. In vitro studies demonstrated specific and sensitive binding of MORAb-004 to MS1 mouse endothelial cells expressing hTEM1, with no binding to control MS1 cells. (125)I-MORAb-004 and (124)I-MORAb-004 both had an immunoreactivity of approximately 90%. In vivo biodistribution experiments revealed rapid, highly specific and sensitive uptake of MORAb-004 in MS1-TEM1 tumors at 4 h (153.2 ± 22.2 percentage injected dose per gram [%ID/g]), 24 h (127.1 ± 42.9 %ID/g), 48 h (130.3 ± 32.4 %ID/g), 72 h (160.9 ± 32.1 %ID/g), and 6 d (10.7 ± 1.8 %ID/g). Excellent image contrast was observed with (124)I-immuno-PET. MORAb-004 uptake was statistically higher in TEM1-positive tumors than in control tumors. Binding specificity was confirmed by blocking studies using excess nonlabeled MORAb-004.
CONCLUSION: In our preclinical model, with hTEM1 exclusively expressed on engineered murine endothelial cells that integrate into the tumor vasculature, (124)I-MORAb-004 displays high tumor-to-background tissue contrast for detection of hTEM1 in easily accessible tumor vascular compartments. These studies strongly suggest the clinical utility of (124)I-MORAb-004 immuno-PET in assessing TEM1 tumor-status.
Keywords
Animals, Antibodies, Monoclonal/diagnostic use, Antibodies, Monoclonal/immunology, Antigens, CD/immunology, Blood Vessels/metabolism, Cell Line, Female, Humans, Iodine Radioisotopes/diagnostic use, Isotope Labeling, Mice, Neoplasm Proteins/immunology, Neoplasms/blood supply, Positron-Emission Tomography/methods
Pubmed
Web of science
Open Access
Yes
Create date
03/03/2015 18:28
Last modification date
20/08/2019 13:28
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