Polyamine-Substituted Gadolinium Chelates: A New Class of Intracellular Contrast Agents for Magnetic Resonance Imaging of Tumors
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- 作者：Markus Wolf ; William E. Hull ; Walter Mier ; Sabine Heiland ; Ulrike Bauder-Wü ; st ; Ralf Kinscherf ; Uwe Haberkorn ; Michael Eisenhut
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：January 11, 2007
- 年：2007
- 卷：50
- 期：1
- 页码：139 - 148
- 全文大小：219K
- 年卷期：v.50,no.1(January 11, 2007)
- ISSN：1520-4804
文摘
A new class of intracellular contrast agents (CA) for magnetic resonance imaging has been developed,based on Gd(DTPA) with two positively charged amide-linked substituents. Uptake of Gd(DTPA) into culturedtumor cell lines (B16 mouse melanoma, MH3924A Morris hepatoma) was below the detection limit whileCA with the melanin-binding pharmacophore 2-(diethylamino)ethylamine reached intracellular concentrationsof ca. 0.03 fmol/cell (ca. 20 
M) for melanoma and 0.02 fmol/cell for hepatoma (24 h at 10 M CA). Withthe polyamine substituents bis(2-aminoethyl)amine or spermidine, CA uptake increased up to 3-fold formelanoma (0.083 fmol/cell) and 9-fold for hepatoma (0.18 fmol/cell). Uptake of polyamine-substituted CAwas reduced by the polyamine transport inhibitor benzyl viologen. Molar relaxivities for three Gd-DTPA-polyamine complexes were in the range 5.6-6.9 for the free complex in solution and 7.7-23.5 s-1 mM-1for Morris hepatoma cell pellets. T1-weighted magnetic resonance imaging at 2.35 T of rats with MH3924Atumors showed contrast enhancement in tumor at 1 and 24 h postinjection of polyamine-substituted CA.
M) for melanoma and 0.02 fmol/cell for hepatoma (24 h at 10 M CA). Withthe polyamine substituents bis(2-aminoethyl)amine or spermidine, CA uptake increased up to 3-fold formelanoma (0.083 fmol/cell) and 9-fold for hepatoma (0.18 fmol/cell). Uptake of polyamine-substituted CAwas reduced by the polyamine transport inhibitor benzyl viologen. Molar relaxivities for three Gd-DTPA-polyamine complexes were in the range 5.6-6.9 for the free complex in solution and 7.7-23.5 s-1 mM-1for Morris hepatoma cell pellets. T1-weighted magnetic resonance imaging at 2.35 T of rats with MH3924Atumors showed contrast enhancement in tumor at 1 and 24 h postinjection of polyamine-substituted CA.