TY - JOUR
T1 - Dysprosium-DOTA-PAMAM dendrimers as macromolecular T2 contrast agents
T2 - Preparation and relaxometry
AU - Bulte, Jeff W.M.
AU - Wu, Chuanchu
AU - Brechbiel, Martin W.
AU - Brooks, Rodney A.
AU - Vymazal, Josef
AU - Holla, Micha
AU - Frank, Joseph A.
PY - 1998/11
Y1 - 1998/11
N2 - 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 1H 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 were measured at 13 different field strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37δC. 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-1sec-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/Tesla2 for T=. 3 to 37 δ 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.
AB - 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 1H 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 were measured at 13 different field strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37δC. 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-1sec-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/Tesla2 for T=. 3 to 37 δ 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.
KW - Curie spin relaxation
KW - Dendrimers
KW - Dysprosium
KW - Macromolecular contrast media
KW - Relaxometry
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U2 - 10.1097/00004424-199811000-00008
DO - 10.1097/00004424-199811000-00008
M3 - Article
C2 - 9818319
AN - SCOPUS:0032471030
SN - 0020-9996
VL - 33
SP - 841
EP - 845
JO - Investigative radiology
JF - Investigative radiology
IS - 11
ER -