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Docking, synthesis, in-vitro evaluation, and optimization of reaction conditions for direct radiolabeling of CGPRPPC with technetium-99m through the GAGG sequence

Mosayebnia, Monaa; Hajiramezanali, Maliheha; Shahhosseini, Sorayab; Hajiagha Bozorgi, Atefehe; Kobarfard, Farzadc; Rezaeianpour, Sedighehd

doi: 10.1097/MNM.0000000000000901

Objective With respect to the reported promising results of cyclic peptide CGPRPPC in early detection of thrombotic lesions, we developed a practical approach for technetium-99m labeling of this peptide using the Glycine–Alanine–Glycine–Glycine (GAGG) sequence as a chelating moiety.

Materials and methods The peptide conjugated to GAGG was prepared using the solid-phase method. The optimization of radiolabeling conditions was performed on the basis of such variables as incubation time, reaction temperature, pH, and concentration of peptide and stannous chloride. Moreover, the stability and fibrin-binding affinity of the radiolabeled peptide were measured. The peptide–fibrin interactions were analyzed by docking studies using HEX and Auto dock 4.2. Softwares.

Results The amounts of synthesized peptide and stannous chloride required for optimal radiolabeling through GAGG were 10 µmol/l and 5 µg, respectively. The best radiochemical purity% (>93%) was achieved at pH 7–8 within 15 min and a reaction temperature of 37°C. On the basis of in silico and in-vitro results, the GAGG-conjugated CGPRPPC peptide showed better binding affinity versus the HYNIC-conjugated one.

Conclusion We could radiolabel the fibrin-targeting peptide with high radiochemical purity% and stability during a short incubation period without a boiling step. Compared with the HYNIC-conjugated peptide, a higher binding affinity was found. Therefore, the GAGG chelating moiety possesses a considerable potentiality in Technetium 99m labeling of peptides while CGPRPPC maintains its binding properties to thrombotic lesions.

aDepartment of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences

bDepartment of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Protein Technology Research Center

cDepartment of Pharmaceutical Chemistry and Radiopharmacy, School of Pharmacy, Phytochemistry Research Center

dPhytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran

eAlborz University of Medical Sciences, Karaj, Iran

Correspondence to Sedigheh Rezaeianpour, PhD, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Vali-e Asr Avenue, Niayesh Junction, P.O. Box 14155-6153, 19839-63113 Tehran, Iran Tel: +98 912 795 9554; e-mail:

Received June 9, 2018

Received in revised form July 8, 2018

Accepted August 6, 2018

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