Scientists made a version of the peptide ARA-290 that can be tagged with a radioactive metal (technetium-99m) so it lights up on a special heart scan (SPECT). In lab tests it stayed stable, stuck to low‑oxygen heart cells, and in rats it gathered in damaged heart tissue, suggesting it could help doctors spot heart attacks early.

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. 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. <i>In vivo</i> studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. 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). The results of studies, <i>in vitro</i> and <i>in vivo</i>, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia.