DTPA-bis(4-carboxycyclohexyl)amide 상자성 복합체의 자기이완특성에 관한 연구 = The Magnetic Relaxation Properties of DTPA-bis(4-carboxycyclohexyl) amide Paramagnetic Gd-chelates

다국어 초록 (Multilingual Abstract)

Purpose : To evaluate the NMR relaxation properties of newly developed high performance paramagnetic complexes.
Materials and methods : 4-aminomethylcyclohexane carboxylic acid (0.63 g, 4 mmol) was mixed with the suspension solution of DMF (15 mL) and DTPA-bis-anhydride (0.71 g, 2 mmol) to synthesize the ligand. The ligand was then mixed with Gd2O3 (0.18 g, 0.5 mmol) to synthesize Gd-chelate. For the measurement of magnetic relaxivity of paramagnetic compounds, the compounds were diluted to 1mM and then the relaxation times were measured at 1.5T(64 MHz). Inversion-recovery pulse sequence was employed for T1 relaxation measurement and CPMG(Carr-Purcell-Meiboon-Gill) pulse sequence was employed for T2 relaxation measurement. Using MATLAB(Version 7.1) program, T1 magnetic relaxation map, R1 map, T2 magnetic relaxation map and R2 map were developed to represent magnetic relaxation time and magnetic relaxivity as image.
Results : Compared to R1=4.9 mM-1sec-1 and R2= 4.8 mM-1sec-1 of Omniscan (Gadodiamide), which is commercially available paramagnetic MR agent, R1 of SUK090(Gd-C32H74N5O24) was 12.46 mM-1sec-1 and R1 of SUK091(Gd-C34H78N5O24) was 12.77 mM-1sec-1. However, R1 of SUK092(Gd-C30H56N5O17) was decreased to 2.09 mM-1sec-1. In case of R2, SUK090(Gd-C32H74N5O24) was 8.76 mM-1sec-1 and SUK091(Gd-C34H78N5O24) was 7.60 mM-1sec-1 whereas SUK092(Gd-C30H56N5O17) was decreased to 1.82 mM-1sec-1.
Conclusion : Among three new paramagnetic complexes, SUK090(Gd-C32H74N5O24) and SUK091(Gd-
C34H78N5O24) showed higher T1, T2 magnetic relaxation rates than that of commercially available paramagnetic MR agent and thus expected to have more contrast enhancement effect.

국문 초록 (Abstract)

목적 : 새로 개발한 상자성 복합체의 자기이완 특성을 조사해 보고자 하였다.
대상 및 방법 : DMF(15 mL)와 DTPA-bis-anhydride(0.71 g, 2 mmol)의 서스펜션 용액에 4-aminomethylcyclohexane carboxylic acid(0.63g, 4 mmol)를 넣어 리간드를 합성한 후 Gd2O3(0.18 g, 0.5 mmol)을 넣어 최종적인 Gd 착화물을 합성하였다. 상자성 복합체의 자기이완율을 측정하기 위해 상자성 복합체를 3차 증류수를 사용하여 1 mM로 희석시켰으며 1.5T(64 MHz)에서 자기이완 시간을 측정하였다. T1 자기이완시간을 측정하기 위하여 반전 회복(inversion-recovery) 펄스열을 사용하였으며 T2 자기이완시간은 CPMG(Carr-Purcell-Meiboon-Gill) 펄스열을 사용하였다. 자기이완 시간 및 자기이완율을 영상으로 표현한 T1 자기이완 지도, R1 지도, T2 자기이완 지도 및 R2 지도를 구현 하였다.
결과 : 현재 시판중인 상자성 조영제인 Omniscan(Gadodiamide)의 R1 = 4.9 mM-1sec-1, R2 = 4.8 mM-1sec-1에 비해 R1의 경우 SUK090(Gd-C32H74N5O24)는 12.46 mM-1sec-1, SUK091(Gd-C34H78N5O24)는 12.77 mM-1sec-1의 값을 나타낸 반면 SUK092(Gd-
C30H56N5O17)는 2.09 mM-1sec-1로 자기이완율이 감소하였다. R2의 경우 SUK090(Gd-C32H74N5O24)는 8.76 mM-1sec-1, SUK091(Gd-C34H78N5O24)는 7.60 mM-1sec-1의 값을 나타낸 반면 SUK092(Gd-C30H56N5O17)는 1.82 mM-1sec-1로 감소 하였다.
결론 : 본 연구에서 합성한 상자성 복합체중 SUK090(Gd-C32H74N5O24)와 SUK091(Gd-C34H78N5O24)는 기존의 상자성 조영제에 비해 T1, T2 자기이완율이 크고 결과적으로 T1/T2 조영증강 효과가 클 것으로 예상된다.

참고문헌 (Reference)

1 "The ef-fects of iron oxides on proton relaxivity" 6 : 647-653, 1988

2 "The detailed synthesis process and characterization are inpreparation as a separate manuscript"

3 "Specific targeting of folate-dendrimer MRI contrast agents tothe high affinity folate receptor expressed in ovarian tumorxenografts" 12 : 104-113, 2001

4 "Plasma pharma-cokinetics,tissue distribution and excretion of MnDPDP in therat and dog after intravenous administration" 38 : 690-699, 1997

5 "Pharmacokinetics of Gadomer-17, a new den-dritic magnetic resonance contrast agent" 12 (12): 128-34, 2001

6 "Organ- and tissue-directed MRIcontrast agents" W.B. Saunders 192-220, 1996

7 "New directions in the development of MR imagingcontrast media" 183 : 1-11, 1992

8 "Molecular imaging of angiogenesis in early-stageatherosclerosis with alpha(v)beta3-integrin-targeted nanoparti-cles" 108 : 2270-2274, 2003

9 "Magnetic resonance contrast media:Principlesand Progress" 6 (6): 65-84, 1990

10 "MRI detection ofearly endothelial activation in brain inflammation" 51 : 248-252, 2004

11 "MR imaging of the breast with Gd/DTPA: useand limitations" 171 (171): 95-103, 1989

12 "ICAM-1 expression in autoimmune encephalitis vi-sualized using magnetic resonance imaging" 104 : 1-9, 2000

13 "ContrastAgents for MRA:Future Directions" 10 : 314-316, 1999

14 "Contrast agents" 5 : 223-240, 1997

15 "Contrast agents" Mosby-Year Book 372-437, 1992