| Objective:The purpose of this study was to investigate the feasibility of using 99mTc labeling Gd-DTPA-BMA which is a contrast enhancer in magnetic resonance imaging (MRI), and to study on the bio-distribution and imaging characteristics by animal experimentations. Another purpose of this study was to provide the basis of 99mTc-Gd-DTPA-BMA using as a potential SPECT/MRI dual-modality agent. Methods:The labeled compounds were prepared by reducing 99mTc in the presence of Gd-DTPA-BMA and Gd-DTPA with stannous chloride (SnCl2), respectively. The best reaction condition was selected through adjusted the ration of Gd-DTPA-BMA and SnCl2, pH, temperature. The radiochemical purity was determined by thin layer chromatography (TLC). Its stability was observed at room temperature. The in vivo bio-distribution in nude mice was observed by the percentage of the injected dose per gram of tissues mass (%ID/g). The 99mTc-Gd-DTPA-BMA diluted with normal saline, containing about 99mTc 185.0 kBq/0.1 ml, was injected into nude mice intravenous. The percentage of the injected dose per gram of tissues mass (%ID/g) was measured at 1 min, 5 min,10 min,30 min,60 min,120 min and 240 min after injection of the labeled compound. Compared with 99mTc-DTPA, renal dynamic scintigraphy in rabbits were performed by SPECT. Three rabbits were injected 99mTc-Gd-DTPA-BMA and 99mTc-DTPA through auricular vein, containing about 99mTc 14.8 MBq/0.2 ml, respectively. The uptake percentage (Uptake%), time to peak (Tmax) and time from peak to 1/2 peak (T1/2) were observed by renal dynamic scintigraphy. The plasma protein binding rate of labeled compounds in rabbit plasma were measured by the trichloroacetic acid (TCA) precipitation method. Compared with Tc-Gd-DTPA and 18F-FDQ the cellular uptake ratio of 99mTc-Gd-DTPA-BMA was observed in human lung cancer A549 cell. The 99mTc-Gd-DTPA-BMA, containing about 99mTc 14.8 MBq/Gd(III) 0.004 mmol, was injected into nude mice bearing A549 tumor. Scintigraphy and MR imaging were performed, respectively. Results:The radiochemical purity of 99mTc-Gd-DTPA-BMA was 99.2%, and stable at room temperature or 37℃blood serum within 6 h more than 92.0%. The in vivo bio-distribution experiment of 99mTc-Gd-DTPA-BMA in nude mice showed that the uptake of the blood was the highest level at 1 min after injection of 99mTc-Gd-DTPA-BMA. All of the major organs, the highest uptake organ was kidney at 5 min. Heart, liver, spleen and lung have a little distribution of radiopharmaceuticals, and brains have the lowest level uptake (%ID/g<1%·g-1). The uptake of the tumor tissue at 1 min after injection of the labeling compound was 12.17±0.82%·g-1. Renal dynamic scintigraphy in rabbits showed that 99mTc-Gd-DTPA-BMA and 99mTc-DTPA were excreted by the kidney, but Tmax and Tm of 99mTc-Gd-DTPA-BMA group were longer than 99mTc-DTPA group (P<0.05). The plasma protein binding rate of 99mTc-Gd-DTPA-BMA and 99mTc-Gd-DTPA were 5.44±0.52% and 5.65±0.28%, respectively, and there was not significantly difference of two groups (P>0.05). The cellular uptake ratio of 99mTc-Gd-DTPA-BMA group was significantly lower than 18F-FDG group at 0.5 h,1 h,2 h after incubating in A549 cells (P<0.05), but there was not significantly difference with 99mTc-Gd-DTPA group (P>0.05). After inject 99mTc-Gd-DTPA-BMA, scintigraphy and MR imaging can clearly show the tumor tissue. 99mTc-Gd-DTPA-BMA group has the highest T/NT (2.57±0.47) at 10 min after injection. It was significantly higher than 99mTc-Gd-DTPA group at 5 min,10 min,20 min (P<0.05), but there was not significantly difference at 30 min,60 min,120 min (P>0.05). The SNR and CNR of 99mTc-Gd-DTPA-BMA group was not significantly difference with 99mTc-Gd-DTPA group at any time (P>0.05). Conclusions:The study indicated that the methods of 99mTc labeled Gd-DTPA-BMA have high labeling efficiency and stability.99mTc-Gd-DTPA-BMA has high uptake in tumor tissue. It was major excreted by the kidney. The imaging of SPECT and MRI in nude mice bearing A549 tumor was clearly. As a potential dual-modal imaging agent,99mTc-Gd-DTPA-BMA is worthy of further research.
|
PDF Full Text Request