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Cellular Delivery of MRI Contrast Agents

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1 Cellular Delivery of MRI Contrast Agents
Matthew J Allen, Keith W MacRenaris, P.N Venkatasubramanian, Thomas J Meade  Chemistry & Biology  Volume 11, Issue 3, Pages (March 2004) DOI: /j.chembiol

2 Figure 1 Synthesis of Polyarginine-Containing Lanthanide Chelates
(a) (1) Piperidine, DMF (2) Fmoc-R(Pbf)-OH, HATU, DMF, DIPEA; (b) (1) piperidine, DMF (2) DOTA(tris-t-Bu ester), HATU, DMF, DIPEA (3) 95% TFA, 2.5% H2O, 2.5% TIS; (b) Eu(OH)3 or Gd(OH)3 in water at 80°C for 12 hr. Chemistry & Biology  , DOI: ( /j.chembiol )

3 Figure 2 Demonstration of the Dependence of Uptake of 4–6 on Incubation Concentration After incubation, NIH/3T3 cells were rinsed with DPBS, treated with trypsin, dissolved in nitric acid, and analyzed with ICP-MS. The graphs show uptake per cell plotted against incubation concentration. Error bars represent one standard deviation. Chemistry & Biology  , DOI: ( /j.chembiol )

4 Figure 3 Washout Rate of 4–6 from NIH/3T3 Cells as a Function of the Number of Rinses Cells were incubated for 1 hr, and then medium was changed. After each rinse period, the medium was removed and analyzed using ICP-MS. Long incubation times were 24, 48, 72, and 96 hr. Short incubation times were 1, 3, 6, and 10 hr. Error bars represent one standard deviation. Chemistry & Biology  , DOI: ( /j.chembiol )

5 Figure 4 Cell-Type Specificity for 7–9
Cells were incubated with compound for 1 hr and rinsed with DPBS, treated with trypsin, dissolved in nitric acid, and analyzed with ICP-MS. The graph shows uptake per cell for each cell type plotted against complex. Incubation concentration of 7-9 was constant within each group of cells but was not constant from compound to compound. Error bars represent one standard deviation. Chemistry & Biology  , DOI: ( /j.chembiol )

6 Figure 5 Results of T1 Study of NIH/3T3 Cells Incubated with 0.3 mM 4, 5, 6, and Gd(III) DO3A (1,4,7-Tris-Carboxymethyl-1,4,7,10-Tetraazacyclododecane) After incubation, cells were rinsed with DPBS. T1 values were measured at 60 MHz and 37°C. The graph depicts the percent change in T1 from untreated NIH/3T3 cells. Values for GdDO3A are from [28]. Error bars represent one standard deviation. Chemistry & Biology  , DOI: ( /j.chembiol )

7 Figure 6 T1-Weighted Spin-Echo MR Images of NIH/3T3 Cells at 9.4 T
Images were obtained using a spin-echo pulse sequence with TR 500 ms, echo delay time (TE) 16 ms. (A) NIH/3T3 cells incubated with 4. (B) Untreated NIH/3T3 cells. (C) Deionized water in a capillary tube as a spatial marker. The scale bar represents 1.2 mm. Chemistry & Biology  , DOI: ( /j.chembiol )


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