Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors.
Epidermal growth factor radiopharmaceuticals: 111In chelation, conjugation to a blood-brain barrier delivery vector via a biotin-polyethylene linker, pharmacokinetics, and in vivo imaging of experimental brain tumors.
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表皮生长因子放射性药物：111通过生物素-聚乙烯接头螯合、缀合至血脑屏障递送载体、药代动力学和实验性脑肿瘤的体内成像。
DOI：
10.1021/bc980123x
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发表时间：
1999
影响因子：
4.7
通讯作者：
W. Pardridge
中科院分区：
文献类型：
--
作者：
A. Kurihara;Y. Deguchi;W. Pardridge
Epidermal growth factor (EGF) is a potential peptide radiopharmaceutical for detection of brain tumors, because many human gliomas overexpress the EGF receptor (EGFR). The transport of EGF to the brain, however, is restricted by the blood-brain barrier (BBB). The purpose of the present study was to develop a vector-mediated brain delivery system for radiolabeled EGF. Human EGF was monobiotinylated with NHS-PEG3400-biotin, where NHS is N-hydroxysuccinimide and PEG3400 is poly(ethylene glycol) of 3400 Da molecular mass. EGF-PEG3400-biotin was radiolabeled with either 125I or 111In through the metal chelator, diethylenetriaminepentaacetic acid (DTPA). The radiolabeled EGF was then conjugated to a BBB delivery vector comprised of a complex of the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which was coupled to streptavidin (SA). Following intravenous injection in rats, the 125I conjugate was rapidly degraded in vivo, while the 111In conjugate was metabolically stable. The brain delivery of [111In]DTPA-EGF-PEG3400-biotin was enabled by conjugation with OX26/SA and was optimized by co-injection of unlabeled EGF to saturate EGF receptors in the liver. The specific binding of the [111In]DTPA-EGF-PEG3400-biotin conjugated to OX26/SA to the EGF receptor was confirmed in C6 rat glioma cells, which had been transfected with a gene encoding for the human EGF receptor under the regulation of a dexamethasone-inducible promoter. In vivo studies of C6-EGFR experimental tumors in Fischer 344 rats demonstrated successful brain imaging only when the peptide radiopharmaceutical was conjugated to the BBB delivery system, although the C6-EGFR tumors did not express EGFR in vivo. In conclusion, these studies describe the molecular formulation of a peptide radiopharmaceutical that can be used for imaging brain tumors behind the BBB.
影响因子：
4
作者：
Blasberg,RG;Groothuis,DR
通讯作者：
Groothuis,DR
使用中性亲和素可改善与亲和素-单克隆抗体缀合物结合的生物素的药代动力学和脑递送。
DOI：
--
发表时间：
1994
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Kang,YS;Pardridge,WM
通讯作者：
Pardridge,WM
DOI：
10.1073/pnas.84.19.6899
发表时间：
1987-10-01
影响因子：
11.1
作者：
WONG, AJ;BIGNER, SH;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B