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Comparative Study
. 2010;49(2):346-50.
doi: 10.1002/anie.200905133.

Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent

Zhiliang Cheng  1 , Daniel L J Thorek, Andrew Tsourkas
Affiliations
Comparative Study

Gadolinium-conjugated dendrimer nanoclusters as a tumor-targeted T1 magnetic resonance imaging contrast agent

Zhiliang Cheng et al. Angew Chem Int Ed Engl. 2010.
No abstract available

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Figures

Figure 1
Figure 1
Schematic diagram illustrating paramagnetic targeted dendrimer nanoclusters (DNCs). Nanoclusters were fabricated by crosslinking polyamidoamine (PAMAM) dendrimers (G5) using a bifunctional amine-reactive crosslinker. Following DNC formation, paramagnetic Gd3+ ions were conjugated to DNCs via DTPA. The resulting paramagnetic DNCs were further functionalized with the tumor-targeting ligand folic acid and the fluorescence dye FITC.
Figure 2
Figure 2
Relaxivity (R1) measurements for Gd-labeled DNCs and Gd-DTPA. T1 measurements were acquired with a Bruker mq60 MR relaxometer operating at 1.41 T (60 MHz) at 40 °C.
Figure 3
Figure 3
Cellular uptake of fluorescently labeled DNCs. Phase contrast and fluorescent images of (A&B) untreated KB cells; (C&D) KB cells following 2 hours incubation with FITC-labeled DNCs. The DNCs are also labeled with folic acid and Gd-DTPA; (E&F) KB cells following 2 hours incubation with FITC-labeled DNCs in the presence of 5 mM free folic acid.
Figure 4
Figure 4
Magnetic resonance images of nude mice with subcutaneous tumor xenografts at various time points following the intravenous injection of Gd-contained nanoparticles. The local hyperintensity generated by the Gd-contained nanoparticles was visualized using a 4.7 T small animal MR. The top row shows mice with KB cell tumor xenografts before and after i.v. injection with folate receptor-targeted DNCs. The middle row shows mice with KB cell tumor xenografts before and after i.v. injection with folate receptor-targeted DNCs in the presence 50 mM free folic acid (FA). The third row shows mice with KB cell tumor xenografts before and after i.v. injection with folate receptor-targeted, Gd-labeled dendrimers (individual dendrimers, G5). The bottom row shows mice with T6-17 cell tumor xenografts (i.e. folate receptor-negative) before and after i.v. injection with folate receptor-targeted DNCs. Images were acquired pre-injection and 1, 4 and 24 hr post-injection. White arrow shows location of tumor.
Figure 5
Figure 5
Quantitative analysis of MR images. The average MR signal intensity (SI) was measured for each tumor and the relative signal enhancement, rSE, was then calculated as the quotient of the SI in the 24 hr post-contrast image and the pre-contrast image. A t-test (two-tailed, unequal variance) was used to compare the rSE for each group of animals. A p<0.05 was considered statistically significant and is indicated by an asterisk.
See this image and copyright information in PMC

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