Shahbazi-Gahrouei Daryoush
Department of Medical Physics and Medical Engineering, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail:
J Res Med Sci. 2009 May;14(3):141-7.
Novel potential MR imaging contrast agents Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP), Gd-hematoporphyrin (Gd-H), Gd-DTPA-9.2.27 against melanoma, Gd-DTPA-WM53 against leukemia and Gd-DTPA-C595 against breast cancer cells were synthesized and applied to mice with different human cancer cells (melanoma MM-138, leukemia HL-60, breast MCF-7). The relaxivity, the biodistribution, T(1) relaxation times, and signal enhancement of the contrast agents are presented and the results are compared.
After preparation of contrast agents, the animal studies were performed. The cells (2×10(6) cells) were injected subcutaneously in the both flanks of mice. Two to three weeks after tumor implantation, when the tumor diameter was 2-4 mm, mice were injected with the different contrast agents. The animals were sacrificed at 24 hr post IP injection followed by removal of critical organs. The T(1) relaxation times and signal intensities of samples were measured using 11.4 T magnetic field and Gd concentration were measured using UV-spectrophotometer.
For Gd-H, the percent of Gd localized to the tumors measured by UV-spect was 28, 23 and 21 in leukemia, melanoma and breast cells, respectively. For Gd-TCP this amount was 21%, 18% and 15%, respectively. For Gd-DTPA-9.2.27, Gd-DTPA-WM53 and Gd-DTPA-C595 approximately 35%, 32% and 27% of gadolinium localized to their specific tumor, respectively.
The specific studied conjugates showed good tumor uptake in the relevant cell lines and low levels of Gd in the liver, kidney and spleen. The studied agents have considerable promise for further diagnosis applications of MR imaging.
合成了新型潜在磁共振成像造影剂钆-四碳硼烷甲氧基苯基卟啉（Gd-TCP）、钆-血卟啉（Gd-H）、抗黑色素瘤的钆-二乙三胺五乙酸-9.2.27（Gd-DTPA-9.2.27）、抗白血病的钆-二乙三胺五乙酸-WM53（Gd-DTPA-WM53）以及抗乳腺癌细胞的钆-二乙三胺五乙酸-C595，并将其应用于接种不同人类癌细胞（黑色素瘤MM-138、白血病HL-60、乳腺癌MCF-7）的小鼠。介绍了造影剂的弛豫率、生物分布、T1弛豫时间和信号增强情况，并对结果进行了比较。
制备造影剂后，进行动物研究。将细胞（2×10⁶个细胞）皮下注射到小鼠的双侧胁腹。肿瘤植入后两到三周，当肿瘤直径为2 - 4毫米时，给小鼠注射不同的造影剂。腹腔注射后24小时处死动物，随后取出关键器官。使用11.4 T磁场测量样品的T1弛豫时间和信号强度，使用紫外分光光度计测量钆浓度。
对于Gd-H，通过紫外分光法测得的钆在白血病、黑色素瘤和乳腺癌细胞中定位于肿瘤的百分比分别为28%、23%和21%。对于Gd-TCP，该数值分别为21%、18%和15%。对于Gd-DTPA-9.2.27、Gd-DTPA-WM53和Gd-DTPA-C595，分别约有35%、32%和27%的钆定位于其特定肿瘤。
所研究的特定缀合物在相关细胞系中显示出良好的肿瘤摄取，且肝脏、肾脏和脾脏中的钆含量较低。所研究的造影剂在磁共振成像的进一步诊断应用方面具有很大的前景。
