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Synthesis and Evaluation of 99Mtc-Dota-Ara-290 As Potential Spect Tracer for Targeting Cardiac Ischemic Region Publisher



Mohtavinejad N1 ; Hajiramezanali M2 ; Akhlaghi M3 ; Bitarafanrajabi A4, 5 ; Gholipour N1, 6
Authors
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Authors Affiliations
  1. 1. Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran
  2. 2. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Cardiovascular Interventional Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran

Source: Iranian Journal of Basic Medical Sciences Published:2021


Abstract

Objective(s): Myocardial infarction caused by ischemia of heart tissue is the main reason for death worldwide; therefore, early detection can reduce mortality and treatment costs. Erythropoietin (EPO) has protection effects on ischemic tissue due to nonhematopoietic peptide (pHBSP; ARA-290) which is derived from the B-subunit of EPO. Materials and Methods: We designed and synthesized a modified DOTA-(Lys-Dabcyl6, Phe7)-ARA-290 using Fmoc solid-phase peptide synthesis strategies. To improve serum stability, Fmoc-Lys-(Dabcyl)-OH as lipophilic amino acid was synthesized along with Fmoc-Phe-OH which then were substituted with Arg6 and Ala7, respectively; they were then investigated for the ability to detect ischemic cardiac imaging. DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 was labeled with technetium 99m, and its radiochemical purity (RCP), stability in the presence of human serum and, specific bind to hypoxic H9c2 cells were evaluated. In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. Results: Radiolabeling purity was obtained more than 96% by ITLC, and in vitro stability of the radiopeptide up to 6 hr was 85%. The binding of 99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr). Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr). Conclusion: The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia. © 2021 Mashhad University of Medical Sciences. All rights reserved.
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