Tm-DOTMA, 2126179-30-2,化学式：TmC₂₀H₃₃N₄O₈•4H₂O

Tm-DOTMA, 2126179-30-2,化学式：TmC₂₀H₃₃N₄O₈•4H₂O

 结构式：

     Tm-DOTMA, 2126179-30-2,化学式：TmC₂₀H₃₃N₄O₈•4H₂O

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Introduction

Non-invasive temperature monitoring has many direct uses in medicine. MR thermometry techniues based on the chemical shift, relaxation rates and molecular diffusion rate of 1 H water signal suffer from poor thermal resolution. Zhu et al. [1] and we [2] independently developed a non-invasive MR thermometer based on the temperature dependence of hyperfine shifted 1 H signal of the paramagnetic lanthanide plex, Tm-DOTA- . One potential drawback of Tm-DOTA- is low signal-to-noise ratio. In this study, we evaluate the use of lanthanide plexes of a methyl substituted analog of DOTA4-, DOTMA4- for MR thermometry. Aime et al. [3] have explored the utility of Yb-DOTMA- as temperature sensitive imaging probe. DOTMA- has 12 euivalent protons on the four methyl groups and gives three times more intense signal pared to Tm-DOTA- . In addition, the methyl proton signals have longer T2 and narrower line-widths because of fast free rotation of the CH3 - groups and reduced through-bond paramagnetic contact interaction.

Experimental

LnDOTMA- were synthesized from Ln2O3 (Ln = Pr, Yb, Tb, Dy and Tm) and Na4DOTMA. 1 H spectra of the LnDOTMA- plexes were acuired in the temperature range 22 to 55˚C using a Varian 9.4 T 89 mm vertical bore MR system. 1 H spin-lattice (T1) and spin-spin (T2) relaxation times of the methyl resonances from the five LnDOTMA- plexes were measured at 37o C. To determine the effects of pH and Ca2+, on the chemical shift of the methyl resonance of the Tm-DOTMA- , the experiments were conducted at 37˚C at five different pH values (3 to11) and five different Ca2+ concentrations (0 to 3 mM). In vivo temperature measurements were performed on subcutaneously (sc) implanted RIF-1 tumor in C3H/HeN mice using a 1 cm diameter surface coil placed over the tumor. 1-2 mmole of Tm-DOTMA- per kilogram body weight was injected through a tail vein. Animal core body temperature was monitored with a rectal fiber-optic temperature probe. The animal temperature was manipulated over temperature ranging from 35 to 40o C by blowing warm air into the magnet bore.

Results and Discussion

Figure 1 shows the structure and 1 H MR spectra of Tm-DOTA- and Tm-DOTMA- showing H1 and H6 or methyl proton signals. The SNR advantage with Tm-DOTMA- is clearly apparent in the spectra. Table 1 shows the chemical shifts, temperature coefficients of chemical shift (CT), line-widths and relaxation times for the methyl resonance from the five plexes. Tb(III), Dy(III), and Tm(III) plexes of DOTMA4- show two resonances because of the presence of two conformational isomers. The relative amount of the minor isomer of Tm-DOTMA- is < 4%. The CT value is the largest for the methyl signal from Tm-DOTMA- . The ratio of temperature coefficient and resonance full width at half height (|CT|FWHH) is also largest for Tm-DOTMA- , therefore, this plex was further evaluated. The methyl proton chemical shifts of Tm-DOTMA- are independent of the pH, Ca2+ concentration or presence of any blood plasma. The proton T1 and T2 values for the methyl resonance of Tm-DOTMA- at 37˚C and 9.4 T are 5.3 and 4.1 ms, respectively. These values are approximay two times more pared to the H6 signal from Tm-DOTA- . These data clearly show the advantages of Tm-DOTMA- over Tm-DOTA- . Figure 2 shows representative in vivo 1 H spectra of Tm-DOTMAfrom a sc-implanted RIF-1 tumor. The tumor temperature was always lower than the core body temperature. This demonstrates that Tm-DOTMA- allows robust measurement of temperature in sc implanted tumors and other tissue in intact animals.

Conclusion

The major advantages of Tm-DOTMA- for MR studies include 1) ~60 times more sensitivity to temperature than water and 15 times more than YbDOTMA- ; 2) more intense signal and longer T2 pared to Tm-DOTA- [1,2]; and 3) insensitivity to changes in concentration, pH, [Ca2+] and presence of other ions and macromolecules. These properties should make Tm-DOTMA- useful for MR thermometry in a wide range of applications. 

Tm-DOTMA, 2126179-30-2,化学式：TmC₂₀H₃₃N₄O₈•4H₂O