| objective:The aim of the study was to investigate the feasibility of using 99mTc labeling gadolinium diethylenetrianinephe-taacetic (Gd-DTPA) and Gd-DTPA-Dimeglumine, which are a contrast enhancer in magnetic resonance imaging (MRI), to find the appropriate condition of reaction, to study basic biologic characteristics of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine by animal experimentations in vitro and in vivo study, furthermore, try to find a novel multimodality imaging agent for SPECT/MRI scan. Methods:The labeled compounds were prepared by reducing 99mTc in the presence of Gd-DTPA or Gd-DTPA-Dimeglumine with Stannous Chloride (SnCl2), respectively. The best reaction condition was selected through adjusted the ration of Gd-DTPA or Gd-DTPA-Dimeglumine and SnCl2, pH, time and temperature. Radiochemical purity and the stability of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine were measured by thin thin layer chromatography (TLC). The plasma protein binding (PPB) rate of labeled compounds in rabbit was measured by the Trichloroacetic Acid (TCA) precipitation method. Ninety healthy Kunming mice were divided randomly into three groups and given intravenous injections of 99mTc-DTPA-Gd,99mTc-Gd-DTPA-Dimeglumine, and 99mTc-DTPA, respectively. The in vivo bio-distribution in mice of each groups were observed by the percentage of the injected dose per gram of tissues mass (%ID/g) of blood sampling and other major organs that were taken out from mice at lmin,5min, 10min,15min,30min, and 60min after intravenous injection of the labeled compounds, respectively. Renal dynamic scintigraphies in rabbits were performed by intravenous injection of 99mTc-DTPA-Gd,99mTc-Gd-DTPA-Dimeglumine, respectively, and to observe the distribution and excretion of each radiopharmaceutical. The imaging characteristics of nude mice bearing lung cancer A549 were observed by scintigraphy and MRI scan after 99mTc-DTPA-Gd, 99mTc-Gd-DTPA-Dimeglumine injection, respectively. All of the experimentations were compared with 99mTc-DTPA. Results:The labeling rate of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine were 98.7%,97.0%, respectively, in the condition of temperature of 45-60℃and incubation of 30 min. Stability of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine at room temperature could be maintained within 6h (radiochemical purity more than 92%). The plasma protein binding rate of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine were 3.80±0.25% and 2.25±0.21%, respectively, and have significant difference (p<0.05). The bio-distribution in mice experiments showed that the uptake of the blood and kidney were the highest level at 1min after injection of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine. The%ID/g of the major organs decreased more than 50% at 5min after injection. The depositions of almost all major organs were less than 1%at 30-60min after injection of 99mTc-DTPA-Gd or 99mTc-Gd-DTPA-Dimeglumine, receptively. Heart, liver, spleen and lung have a little distribution of radiopharmaceuticals, and brains have the lowest level uptake (%ID/g＜1). Renal dynamic scintigraphy in rabbits showed that 99mTc-DTPA-Gd,99mTc-Gd-DTPA-Dimeglumine and 99mTc-DTPA were quickly excreted by the kidney. The time to peak is about 5min. The half time of clearance is about 15min. The tumor tissues in A549 bearing nude mice have the obvious retention after injection of 99mTc-DTPA-Gd (T/NT=2.1,1.5h) or 99mTc-Gd-DTPA-Dimeglumine (T/NT=3.4,1.5h) by scintigraphy, even in 99mTc-DTPA group. MR enhancement scan showed that the edge of tumor was partly contrasted in A549 bearing nude mice after intravenous injection of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine. Conclusions:The study indicated that the methods of 99mTc labeled Gd-DTPA analogues are simple and have high labeling efficiency. It is a significant way that these radiopharmaceuticals can be administrated in vitro and in vivo pharmacokinetics experimentations, which not only to study its bio-distribution in animal but also to directly observe its distribution and excretion by renal dynamic scintigraphy. The biodistribution and excretion of 99mTc-DTPA-Gd and 99mTc-Gd-DTPA-Dimeglumine are similar as that of 99mTc-DTPA. The tumor tissues were obviously displayed by scintigraphy and the edge of tumors were partly contrasted by MR enhancement scan in A549 bearing nude mice after injection of 99mTc-DTPA-Gd or 99mTc-Gd-DTPA-Dimeglumine. The imaging performance of scintigraphy and MRI in A549 bearing nude mice may be result of the changed of microenvironments in tumor tissues. With the foundation of this study, it has the potential hope to prepare a novel multimodality imaging agent for SPECT/MRI scan.
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