Preparation And CT Imaging Of A Novel Bismuth-based Contrast Agent

With the development of medical technology,non-invasive imaging methods are widely used in clinical practice.As one of the most important examination methods,computed tomography(CT)has the advantages of fast scanning speed and high resolution,and plays an important role in clinical diagnosis.Non-enhanced CT can clearly diagnose some diseases such as respiratory diseases,skeletal system diseases,etc.,but the diagnose of most diseases require higher tissue resolution to obtain more imaging information,for example,diseases of abdominopelvic system and diseases of limb muscles,and thus it is necessary to rely on the use of CT contrast agent to identify and make a definitive diagnosis.The contrast agent approved and widely used in clinic practice is non-ionic small molecule iodine contrast agent,but it has the disadvantages of low sensitivity and unpredictable nephrotoxicity.In recent years,more attentions have been paid to the new CT contrast agents based on high atomic number elements,which is charactered by a better X-ray attenuation ability.Among them,bismuth-based materials have outstanding biocompatibility and high contrast CT imaging ability.In addition,bismuth is cheap and abundant in stock,coupled with the easy synthesis and low toxicity characteristics of bismuth-based materials,which make it a potential candidate for new CT contrast agents.The successful preparation of bismuth-based materials is expected to become the supplement and substitute of the existing CT contrast agents.This research is based on bismuth(Bi)and using diethylene triamine pentaacetic acid(DTPA)as the chelating agent to prepare a new bismuth chelate(Bi-DTPA).The research contents are as follows:1.Preparation,characterization and biological characteristics of bismuth diethylenetriamine pentaacetateBased on bismuth trioxide(Bi2O3)and diethylenetriamine pentaacetic acid(DTPA),a chelate compound,bismuth diethylenetriamine pentaacetic acid(Bi-DTPA),was constructed by a simple method and characterized by IR and UV spectra.The biocompatibility of bismuth diethylenetriamine pentaacetate acid in vitro was tested by cell experiment,and the histomorphology of main organs of mice was observed after intravenous injection of bismuth diethylenetriamine pentaacetate to evaluate its biocompatibility in vivo.The distribution of bismuth in vivo was determined by intravenous injection of diethylenetriamine pentaacetic acid bismuth chelate via mice tail,which indirectly reflected the distribution of bismuth in the body.The content of bismuth in blood of mice was determined at a series of time points,which were used to analyze the pharmacokinetic characteristics of bismuth chelate.2.CT imaging of bismuth diethylenetriamine pentaacetate acidIn vitro CT imaging:Bismuth chelate and ioversol solution of the same concentration were prepared.Conventional CT and dual-source CT were used to evaluate the CT imaging effect of the two solutions in vitro.In vivo CT imaging:The imaging effect of bismuth chelate and ioversol solution were compared in Kunming mice.Through constructing mouse model of breast cancer,the CT imaging effect of bismuth chelate was observed in subcutaneous breast cancer.The results are as follows:1.The chelate of bismuth diethylenetriamine pentaacetic acid has good stability and biocompatibility in vitro and in vivo.Its plasma clearance rate follows the first-order elimination kinetics and has a short half-life time.2.Bismuth chelate has good CT imaging ability and X-ray attenuation curve in vitro,which is better than the same concentration of ioversol.It can be used for CT imaging of breast cancer bearing mice.Diethylenetriamine pentaacetic acid bismuth is easy to prepare and has stable structure.It can overcome the shortcomings of non-ionic iodide contrast agents and has better CT imaging performance.Bismuth chelates is a potential candidate for clinical CT new contrast agents.The successful preparation of bismuth chelates provides a research prospect for the development of CT contrast agents with low toxicity,low cost and high contrast.