Synthesis and Radiolabeling of HYNIC-GPRPILE and HYNIC-GPLGAAD Peptides with 99mTc as fibrin imaging agent

Background: Today, Thrombosis is a serious risk factor for both thromboembolic disease (such as DVT, PE) and cancer. Fibrin is a major constituent of clots and is present in all types of thrombi, but absent in circulation. Fibrin is a highly sensitive and specific target for molecular imaging of thrombi. In the present study, we have developed two linear fibrin-binding peptides for thrombus imaging. Peptides were synthesized, radiolabeled with 99mTc and their stability in normal saline and human plasma and LogP were determined.Methods: HYNIC-Gly-Pro-Arg-Pro-ILe-Leu-Glu and HYNIC-Gly-Pro-Lys-Gly-Ala-Ala-Asp peptides were synthesized using a standard Fmoc strategy and radiolabeled with 99mTc. The stability of the radiolabeled peptides in human plasma and normal saline as well as partition coefficient (LogP) was determined.Results: HYNIC-GPRPILE calculated for C41H65N13O11: 915.5; found m/z = 916.5 [M + H] +. Analytical RP-HPLC: Rt = 10min; 85 % A, 15 % B., LogP=-1.83±0.31 HYNIC- GPLGAAD calculated forC31H47N11O11:749.3; found m/z=750.3 [M + H] +. Analytical RP-HPLC: Rt = 8min; 85 % A, 15 % B, LogP=-2.58±0.51 The optimal labeling conditions were 20 μg peptide, 80° C, pH 5 - 6 and incubation time 30 min. The radiochemical purity of radiolabeled peptides was more than 95%. The stability of peptides in human plasma at 37°C was 95 % after 6 h.Conclusions: The results indicate that peptides are promising agents for in vitro and in vivo studies.

کلیدواژه ها:

Thrombosis ، HYNIC ، Fibrin ، 99mTc ، DVT