Dysprosium-DOTA-PAMAM dendrimers as macromolecular T2 contrast agents - Preparation and relaxometry

被引:39
作者
Bulte, JWM
Wu, CC
Brechbiel, MW
Brooks, RA
Vymazal, J
Holla, M
Frank, JA
机构
[1] NIH, Lab Diagnost Radiol Res, CC, Bethesda, MD 20892 USA
[2] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA
[3] NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA
关键词
dysprosium; dendrimers; macromolecular contrast media; relaxometry; Curie spin relaxation;
D O I
10.1097/00004424-199811000-00008
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
RATIONALE AND OBJECTIVES. The authors have investigated dysprosium [Dy]-DOTA-PAMAM, generation 5 (G=5) dendrimers as a possible new class of macromolecular T2 contrast agents. The use of DOTA provides a metal complex with greater stability than can be achieved using DTPA as ligand, an important factor in the design of blood pool agents with long half-lives. METHODS. Generation 5 ammonia-core PAMAM dendrimers were linked to the bifunctional ligand p-SCN-Bz-DOTA, After determination of the number of conjugated DOTA molecules by H-1 nuclear magnetic resonance, Dy3+ was titrated at a 90% molar ratio. For comparison, single ionic chelates of Dy-DTPA and Dy-DOTA also were prepared. Using a variable field relaxometer, T1 and T2 relaxation times mere measured at 13 different held strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37 degrees C. RESULTS. The synthesis resulted in a preparation with 76 DOTA and 68 Dy3+ ions per dendrimer molecule, The T1 relaxivity values for Dy-DTPA, Dy-DOTA, and the Dy-DOTA-based dendrimer all were independent of field strength, with values between 0.12 and 0.20 mM(-1)sec(-1). At lower fields (0.05-0.1 T), 1/T2 was identical to 1/T1, At higher fields, however, 1/T2 increased quadratically with field strength, with a strong dependence on temperature, The field-dependent component of 1/T2 was up to three times higher for the Dy-DOTA-based dendrimer compared with the single chelate molecules, with coefficients of 0.37 to 0.03 sec(-1)/Tesla(2) for T = 3 to 37 degrees C. CONCLUSIONS. The results are interpreted with the "inner sphere" theory of susceptibility effects (Curie spin relaxation). The large temperature dependence suggests that the dominant mechanism of relaxation is the contact interaction effect, with the proton residence time as the primary time constant, This largely unexplored relaxation mechanism has the potential to create a new class of T2-selective contrast agents.
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页码:841 / 845
页数:5
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