The Synthesis And Characterization Of Magnetic Resonance Imaging Contrast Agent Ligands Based-RGD Peptide

Magnetic resonance imaging (MRI) is an important diagnostics imaging technologyin clinical, and approximately one-third of MRI exams include the use of MRI contrastagent. It is very crucial to design and synthesis the ligands of contrast agent, whosestructures and natures determine the performances of the contrast agent. Currently,skeleton molecules, such as1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) and diethylenetriaminepentacetic acid (DTPA) have been the main choices ofthese ligands. However, the resulted contrast agents have no targeting properties, lowrelaxivity and poor across-membranes. Although many novel ligands based on these twoskeleton molecules have been synthesized, just some one property of the contrast agentgains optimization. To obtain the contrast agent with multiple properties, we imagine thatif some building blocks with different characteristics are conjugated into one molecule,which might have the all characteristics at the same time. So we design and synthesisfour ligands of contrast agents with multiple properties. The organization of the main workis as follows.(1) Two novel Zn(II)-activated MRI contrast agent ligands N,N-bis(tert-butyloxy-carbonylmethyl)-6-aminocaproic acid (compound12) and Bis(2-pyridylmethyl)acetic acid (compound13) were synthesized.(2) By employing the method of SPPS and Arg-Gly-Asp-Phe-Lys (RGDfk) used astargeting unit and DOTA as MRI contrast agents section, a new MRI contrastagent ligand (14) with potential targeting properties and high relaxivity wasdesigned and synthesized. It will mainly be used for the post-contrastmulti-functional performance test.(3) Based on the compound (14) and bispalmityl group used as the part ofacross-membranes, compound (15) with potential targeting properties and highrelaxivity and good across-membranes was synthesized.(4) Based on the compounds (14),(12) and (13), two kinds of novel contrast agentligands (16) and (17) with potential targeting properties, high relaxivity andZn(II)-activated were designed. Compound (16) has been synthesized, while compound (17) is on the way.