Synthesis and evaluation of ^99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region.

Mohtavinejad N, Hajiramezanali M, Akhlaghi M, Bitarafan-Rajabi A, Gholipour N

Iranian journal of basic medical sciences1 Nov 2021Cited by 3 (Europe PMC)

PMID35317117PMCIDPMC8917853DOI10.22038/ijbms.2021.57565.12799PepBankPUB-35317117

Summary

ObjectivesMyocardial 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 methodsWe 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.ResultsRadiolabeling 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).ConclusionThe 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone4

In this study, Cibinetide (ARA-290) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Cibinetide (ARA-290).

01AnimalNot a test of Cibinetide (ARA-290) aloneAnimal study (in vivo)Pharmacokinetics
In a rat cardiac ischemia model, the labelled modified ARA‑290 radiopeptide accumulated considerably in the ischemic region, with a cardiac ischemic-to-lung rate of 3.65 ID/g % at 0.5 hr.
In plain wordsIn rats with heart ischemia, the labelled ARA‑290 tracer collected in the injured heart area.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseRadiopeptide accumulation in ischemic region
Study
ratn: not reported in source
Normal and cardiac ischemia rat model
Outcome group
Pharmacokinetics · Cardiovascular
Measurements
Cardiac ischemic-to-lung rate
3.65 ID/g %
0.5 hr
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model.
In this study, Cibinetide (ARA-290) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cibinetide (ARA-290).
Show in the study text Report a problemFND-3531711704
02LabNot a test of Cibinetide (ARA-290) aloneIn vitro (cells)Activity measurement
The labelled modified ARA‑290 radiopeptide bound hypoxic H9c2 cells about 3 times more than normoxic cells at 1 hr.
In plain wordsIn cells, the labelled ARA‑290 tracer bound about 3 times more to oxygen-starved cells than to normal cells.
Peptide
Cibinetide (ARA-290)
Outcome
IncreaseBinding of radiopeptide to hypoxic cells
Study
n: not reported in source
Hypoxic versus normoxic H9c2 cells
Comparator
Normoxic cells
Outcome group
Receptor activity and mechanism · Cardiovascular
Measurements
Binding ratio hypoxic to normoxic
3 fold
1 hr
Source sentences
Summary
The binding of ^99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr).
1 context sentence(design, population, supporting numbers)
Summary · context
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 this study, Cibinetide (ARA-290) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cibinetide (ARA-290).
Show in the study text Report a problemFND-3531711703
03LabNot a test of Cibinetide (ARA-290) aloneIn vitro (cell-free)Other
The technetium-99m labelled modified ARA‑290 radiopeptide reached a radiochemical purity of more than 96% by ITLC.
In plain wordsIn lab tests, the labelled ARA‑290 tracer had a purity above 96%.
Peptide
Cibinetide (ARA-290)
Outcome
Not applicableRadiolabeling purity
Study
n: not reported in source
99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 radiopeptide
Outcome group
Synthesis and manufacturing · Pharmacology
Measurements
Radiochemical purity
> 96%
ITLC
Source sentences
Summary
Radiolabeling purity was obtained more than 96% by ITLC
1 context sentence(design, population, supporting numbers)
Summary · context
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 this study, Cibinetide (ARA-290) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cibinetide (ARA-290).
Show in the study text Report a problemFND-3531711701
04LabNot a test of Cibinetide (ARA-290) aloneIn vitro (cell-free)Other
The labelled modified ARA‑290 radiopeptide had an in vitro stability of 85% in human serum up to 6 hr.
In plain wordsIn lab tests, 85% of the labelled ARA‑290 tracer stayed intact in human serum for up to 6 hours.
Peptide
Cibinetide (ARA-290)
Outcome
Not applicableIn vitro serum stability
Study
n: not reported in source
Radiopeptide in human serum
Outcome group
Synthesis and manufacturing · Pharmacology
Measurements
Stability in serum
85%
up to 6 hr
Source sentences
Summary
in vitro stability of the radiopeptide up to 6 hr was 85%.
1 context sentence(design, population, supporting numbers)
Summary · context
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 this study, Cibinetide (ARA-290) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Cibinetide (ARA-290).
Show in the study text Report a problemFND-3531711702

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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