Preparation and application of Gadolinium diethylenetriamine pentaacetic acid-human serum albumin in MR lymphography / 中国组织工程研究

ABSTRACT

BACKGROUND: The imaging technique of CT and MRI has lower diagnostic accuracy in analyzing lymph node location due to the nonspecific diagnostic criteria. However, this situation can be improved with Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), especially the use of lymphatic targeting contrast agent. OBJECTIVE: To prepare DTPA-coupled human serum albumin (HSA) labeled with gadoliniumion, and to investigate the enhancement for the lymph node in animal experiment, in further, to explore the potential value of its application. DESIGN, TIME AND SETTING: The randomized grouping, controlled animal experiment was performed at the laboratory of Medical Imaging Center, Nanfang Hospital from December 2008 to April 2009. MATERIALS GdCI3 was prepared with Gd2O3 reacted with 0.1mol/L HCI for 10 minutes. Then, DTPA cyclic anhydride and HAS solution were mixed together at the ratio of 2001 or 1001. The product was divided into 4 equal portions, which was reacted with 5.0, 6.0, 7.0, 8.0 pH values at room temperature for 30 minutes. At last, GdCI3 was added. The complexation reaction was completed within 1 minute. The Gd-DTPA-HAS was dried and prepared for Gd-DTPA-HAS solution with concentration of 0.50 mmol Gd/L.METHODS: Six New Zealand rabbits were undergone the MRI examination, followed by subcutaneous injection of 0.2 mL with Gd 0.50 mmol/L HSA-Gd-DTPA solution. And contrast scanning was performed at minutes 30, 60 and 180 after injection. The signal intensity of popliteal lymph node was measured and the enhancement rate was obtained. MAIN OUTCOME MEASURES: The number of combined Gd-DTPA per HSA at different reaction conditions was measured, and coupling efficiency of HSA-DTPA was calculated. The enhancement rates of lymph node, as well as dynamic changes were observed. RESULTS: ①The number and coupling efficiency of HSA-coupled of gadolinium ions were increased with the pH value of the reaction system at the same DTPA-to-HSA molar ratio. ②At the same pH value of the reaction system, the number of HSA-coupled of gadolinium ions increased with the DTPA-to-HSA molar ratios while the coupling efficiency of HSA-coupled of gadolinium ions decreased.③After subcutaneous injection, HSA-Gd-DTPA entered the lymphatic vessel, which resulted in obvious homogeneous enhancement of the lymphatic vessels and popliteal lymph nodes. CONCLUSION: The number and coupling efficiency of HSA-coupled of gadolinium ions can be increased in pH=8.0, 0.1 mol/L NaHCO_3 reaction system. HSA-Gd-DTPA is an effective contrast agent targeted for lymph node after subcutaneous administration.