The Study Of Production Of IFVs Liposome Carrying Gd-DTPA And Its Application In Enhanced MR Imaging Of Rabbit's Liver

Objective:The diagnostic value of liver and spleen in MRI is inferior to that of nerve center and spine. The paramagnetic contrast agent gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA) function as an effective extracellular fluid contrast agent for magnetic resonance(MR) imaging, but early experience with Gd-DTPA as a contrast agent for imaging the liver has been disappointing .Its utility as a liver and spleen contrast agent is diminished by rapid equilibration between intra- and extravascular fluid compartments. Liposomes can be phagocytosed by the reticuloendothelial cells in the liver and spleen .So Gd-containing liposomes can be used as a specific contrast agent of MR for liver and spleen. Interdigitation-fusion vesicles (IFVs) is large unilamellar vesicles and its diameter can be l-6μm.The high initial volume(20-25 M 1/μmol lipid) make it possible to entrap enough Gd-DTPA and to enhance constitution by shortening the T1 relaxation time of MR .We investigate the applying of IFVs(interdigitation-fusion vesicles) liposome carrying Gd-DTPA to enhance the liver of rabbit in MRI.Method:We produced IFVs through the meliorated method to entrap Gd-DTPA. The diameter and enveloping efficiency of IFVs liposome were measured with photon correlation spectroscopy(PCS) and high performance liquid chromatography(HPLC) respectively. DFVs liposome were preserved in enclosed tube at 4℃.IFVs liposome were injected into ear vein of five rabbits(n=5) after diluted with same volume 0.9% saline solution and MR (1.5 T) .image of liver were obtained after 2. 15. 30. 60. 90 minutes and 5 hour. Signal intensity of liver and muscle were measured .Hepatic function of each rabbit were measured before and after IFVs liposome injected. Blank contrast (n= 10) and free Gd-DTPA contrast (n=10) were prepared with the same MR parameter.The VX2 carcinoma was transplanted in liver of the rabbits and was measured in MR2with Gd-DTPA and carrying Gd-DTPA IFVs liposome which diameter is about 3 urn after 1 and 2 week.Result:The diameter of IFVs liposome was l00nm and 3um. Enveloping efficiency was 69+7-5.4% and more higher than other type liposomes. The main artery and kidney was kept enhancing for 1 hour after 100 nm BFVs liposome was injected in ear vein of the rabbits. Liver signal intensity decreased earlier (after injecting IFVs 2minutes) and increased after 15 minutes then keep the level to 60minutes. There were dramatic difference of signal intensity between IFVs liposome and contrast groups (P<0.01) and the signal intensity begin to decrease after 90 minutes. It had returned the level of blank contrast group after 5 hours. The signal intensity of muscle did not increase in all groups. Hepatic functions of the rabbits had no notable difference before and after EFVs were injected. The VX2 carcinoma in the liver was difficult to find with plain scan or enhanced with Gd-DTPA in MR in all the time .But after injected with 3m IFVs liposome 15-30 minutes in the second week, the VX2 tumor could be found easily because the liver around it was enhanced dramatically.Conclution:1. IFVs liposme production: DSPC has good stability and can be used to produce liposome by it. After combined with cholesterol .the fluidity of the liposomeV membrane would be reinforcement .We found there were no dramatic difference between their enveloping efficiency.2. The liposomes which we produced by MFIC have good stability and well-distributed diameter. MFIC is new patent instrument made in USA and it can overcome the flaw of ultrasound fragmentation meter efficiently .It also can enlarge to industrial production and has good application prospect.3. Gd-DTPA can be measured exactly by High Performance Liquid Chromatography (HPLC) device. We fumbled about the detection condition and the best matching of streaming movement phase.4. IFVs liposome carrying Gd-DTPA have good stability and can be stored in refrigeration out the body for long time.5. IFVs liposome carrying Gd-DTPA which diameter is lOOnm could keep enhancing The mai...