Skip to main content

Synthesis and biological evaluation of [131I]iodocarvedilol as a potential radiopharmaceutical for heart imaging


The optimization of the radiolabeling yield of carvedilol with iodine-131 was described. Dependence of the labeling yield of [131I]iodocarvedilol on the concentration of carvedilol, chloramine-T content, pH of the reaction mixture and reaction time was studied in details. Carvedilol was labeled with iodine-131 at pH 6 with a labeling yield of 92.6 ± 2.77% by using 100 µg carvedilol, 200 µg chloramin-T (CAT) and 30 min reaction time. The formed [131I]iodocarvedilol was nearly stable for a time up to one day. Biodistribution of [131I]iodocarvedilol was investigated in experimental animals. [131/123I]iodocarvedilol was located in the heart with a concentration of 19.6 ± 0.41% of the injected dose at 60 min post injection. It has a high heart uptake and heart to liver ratio, both of which are beneficial for high-quality SPECT (single-photon emission computerized tomography) myocardial imaging. [131/123I]iodocarvedilol solve most the drawbacks of the FDA (Food and Drug Administration) approved 99mTc-sestamibi.

Peer Review reports


A blockage of the arteries that supply the heart muscle is known as coronary artery disease (CAD). Chest aches and breathing difficulty are signs of partial blockage, which results in lower blood supply to the heart. A complete obstruction of these veins can cause myocardial infarction by weakening and/or killing portions of the heart tissue caused by a lack of oxygen. The most common kind of heart disease and the major cause of death worldwide for both men and women is coronary artery disease (CAD).

Myocardial perfusion imaging (MPI) is a non-invasive imaging technology that utilizes an intravenously administered radiopharmaceutical to determine the distribution of blood flow in the myocardium during both rest and stress [1, 2].

The radiopharmaceutical must first reach the myocardium, where it must be up taken by live cardiac cells [3, 4].

Myocardial uptake directly relates to flow of blood, high extraction fraction, high target-to-background (T/B) ratio, good myocardial persistence (exhibiting sustained holding in the myocardium) and photon flux [5] where all of the above are desirable ideal features of a perfusion radiopharmaceutical [6].

Thallium-201 (201Tl) and 99mTc-based myocardial perfusion tracers are used in SPECT.

The sodium-potassium adenosine triphosphatase (Na/K-ATPase) pump is responsible for 201Tl extraction in the heart, hence its extraction fraction is influenced by both ATPase function and blood flow [7]. Thallium-201 has a physical half-life of 73 h and emits x-rays with energies of 67–82 KeV and gamma rays with energies of 135–167 KeV.

The picture quality of thallium-201 is worse than that of technetium-labeled agents [8,9,10], which has limited its application [11].

99mTc-Sestamibi, 99mTc-tetrofosmin and 99mTc-teboroxime have been approved by the FDA [12]. They all passively traverse cell membranes and have distinct myocardial accumulation and clearance characteristics. Despite having poor extraction and biodistribution qualities, due to their higher energy photons and low redistribution profiles, all three offer images of higher quality than 201Tl.

In nuclear cardiology, 99mTc-Sestamibi has been frequently utilized for MPI. Owing to its high liver uptake [13] and roll-off at greater blood flow levels, it does not match the criteria of an ideal perfusion imaging tracer.

The high liver uptake makes evaluating cardiac activity in the inferior and left ventricular walls difficult [14].

Photon scattering from significant liver activity remains a major obstacle for successful SPECT diagnosis of heart dysfunction, despite ongoing attempts to eliminate this interference.

As a result, developing a novel perfusion radiopharmaceutical with superior biodistribution and/or extraction capabilities would be extremely beneficial [15,16,17].

Carvedilol is an antihypertensive drug that is used to treat elevated blood pressure and heart failure. It’s also used to boost your chances of survival after a heart attack if heart isn’t working well. Carvedilol binds to β-adrenergic receptors on cardiac myocytes in a reversible manner.

The inhibition of these receptors inhibits the sympathetic nervous system from responding, resulting in a drop-in heart rate and contractility. This action is beneficial in heart failure patients [18] where the sympathetic nervous system is activated as a compensatory mechanism (Fig. 1) [19].

The aim of the present work was to establish a simple and efficient method for radiosynthesis, characterization and biological evaluation of [131I]iodocarvedilol as a potential myocardial perfusion imaging radiopharmaceutical.

Fig. 1
figure 1

Chemical structure of carvedilol


Carvedilol was purchased from Memphis pharmaceutical company; Egypt and all other chemicals were purchased from Merck and they were analytical reagents.

Labeling procedure

Under oxidative circumstances in the presence of CAT, [131I]iodocarvedilol was frequently produced via direct electrophilic substitution with no carrier added (NCA) 131I. NCA 131I allows for the use of high specific activity iodide without the need for carrier iodine.

The effect of different reaction parameters and conditions on radiolabeling efficiency, like the amount of oxidizing agents (CAT), carvedilol concentration [10 to 300 µg, (2.46 × 10− 5 to 7.38 × 10− 4 mM)], reaction pH (3–10), and reaction time (5–120 min), were studied and optimized in order to maximize radioiodination yield. No-carrier-added Na131I (7.2 MBq) was transferred to the reaction flask. A freshly generated CAT in methanol was added to the reaction mixture, followed by 100 µg (2.46 × 10− 4 mM) of carvedilol in methanol. For 15 min, the reaction mixture was agitated using a magnetic stirrer at room temperature. A drop of 10% saturated sodium thiosulfate (10 mg/mL in H2O) was added to breakdown the excess iodine (I2) and stop the reaction by reducing it to iodide (I) as it oxidizes to tetrathionate (S4O62−) [20], [21].

The radioiodinated product was separated, and TLC (Thin Layer Chromatography) was used to determine the radioiodination yield and purity of the product.


Thin-layer chromatography was used to determine the radiochemical yield and purity [22] of [131I]iodocarvedilol utilizing strips of silica gel coated on an alumina sheet.

1–2 µL of the reaction mixture was put 3 cm above the lower edge of a TLC strip (1.5 cm width, 15 cm length) and allowed to evaporate gradually.

HPLC (High-performance liquid chromatography) analysis: The radiochemical yield of [131I]iodocarvedilol was calculated by injecting 10 µL of the reaction mixture into the column Rp-18 (250 mm x 4.6 mm, 5 μm) constructed in the HPLC (Shimadzu model), which contains a set of pumps LC-9 A, Rheohydron injector (Syringe Loading Sample Injector-7125), and UV spectrophotometer detector (SPD-6 A). A mixture of acetonitrile/water (65:35) containing 0.1% trifluoroacetic acid was used as mobile phase, at a flow rate of 1.0 mL/ min. The labeled compound was collected separately by using a fraction collector up to 12 min and its activity was counted by using well a type NaI(Tl) crystal connected to a single-channel analyzer.

Nonradioactive iodination of carvedilol

Carvedilol was labeled with non-radioactive iodine with the chloramine-T method. Iodination of carvedilol generally follows the same chemistry used for radioactive iodination. Carvedilol (100 mg) was dissolved in minimum amount of methanol then a mixture of 200 µg chloramine-T and 15 mg NaI solution was added with vigorously stirring over 60 min for 1.5 h. The reaction products were separated with high performance liquid chromatography. The 1 H-NMR of 127 I-iodocarvedilol is similar to that of the carvedilol itself except the hydrogen in the paraposition to OCH3 phenyl side chain which is different. 1 H-NMR (δ ppm):

8.2 (d, 1 H,a indole ring CH), 7.1 (d, 1 H,b indole ring CH), 7.11 (t, 1 H,c indole ring CH), 7.25 (d, 1 H,d indole ring CH), 11.2 (s, 1 H,e indole ring NH), 6.7 (d, 1 H,f indole ring CH), 7.3 (t, 1 H,g indole ring CH), 7.45 (d, 1 H,h indole ring CH),4.15 (m,3 H, i,j 2 H-methylene CH2 and 1 H-methine CH), 5.2 (d, 1 H,k alcohol OH), 2.8 (m, 2 H,l methylene CH2), 2.1 (s, 1 H,m amine NH), 2.9 (t, 2 H,n methylene CH2), 4 (t, 2 H,o methylene CH2), 6.9 (s, 1 H,p 1-benzene ring), 6.8 (m, 2 H,q,r 1-benzene ring) and 3.7 (s, 3 H,t CH3) as shown in Fig. 2.

Fig. 2
figure 2

Suggested structure of 127I-carvedilol

In vitro stability of [131I]iodocarvedilol

In vitro, the stability of [131I]iodocarvedilol was investigated by combining 1 ml normal serum with 0.5 mL [131I]iodocarvedilol and incubating for 24 h at 37 oC.

During the incubation, 0.2 mL aliquots were taken at varied time intervals up to 24 h and exposed to TLC to determine the percent of [131I]iodocarvedilol and free iodine.

As a result, the radiolabeled compound stability will decide its potential for in vivo application.

Determination of octanol-water partition coefficient (log po/w)

Log P values of [131I]iodocarvedilol was determined using the following procedure: the [131I]iodocarvedilol was prepared and purified by HPLC. The collected mobile phases were evaporated and the residue was dissolved in a mixture of equal volume (3 mL:3 mL) n-octanol and water. After vortex for > 20 min, the mixture was centrifuged at 8,000 rpm for 5 min. Samples (in triplets) from aqueous and n-octanol were obtained and counted separately in a gamma counter. The partition coefficients were calculated using the equation: P = (activity concentration in n-octanol)/ (activity concentration in water). The log P value was measured three different times and reported as an average of three different measurements. The calculated lipophilicity equal to 1.8.

Biological evaluation

The animal experimental protocols followed the Egyptian Atomic Energy Authority’s rules and were approved by the animal ethics committee of the Labeled Compound Department. The biodistribution of [131I]iodocarvedilol was studied in normal rats (purchased from Egyptian National Research Center) (n = 5) after 0.5, 1, and 3 h post injection (pi). Animals were housed in groups of five and given food and water prior to the study. Each animal received an aliquot of 10 µL containing 3.7 MBq of the purified [131I]iodocarvedilol via the tail vein. Each animal was housed separately before being sacrificed by cervical dislocation at 0.5, 1, and 3 h following [131I]iodocarvedilol injection (n = 5). Following sacrifice, each rat was weighed, and blood was collected from the heart and weighed. Muscles, bone, and blood were predicted to contribute for 40, 10, and 7% of total body weight, respectively [23]. Organs and tissues were cleaned with saline, collected in plastic containers, and weighed after dissection. In a well type NaI(Tl) well crystal linked to an SR-7 scaler ratemeter [24], the radioactivity of each sample as well as the background was quantified. For each time point, the percent injected dose (ID) per organ (percent ID/organ S.D.) in a population of five rats is presented. The Student t test was used to assess data differences. The two-tailed test results for p are presented, and all results are given as mean ± SEM. The level of significance was set at p ≤ 0.05.

Results and discussion

TLC was used to determine the radiochemical purity of [131I]iodocarvedilol, with a developing solvent mixture of methylene chloride: ethyl acetate (2:1 v/v), where radioiodide (131I) remained near the origin (Rf = 0–0.5), while [131I]iodocarvedilol moved with the solvent front (Rf = 0.7–1). The percentage radioiodination yield was calculated as the ratio of the radioactivity of [131I]iodocarvedilol to the overall activity, The average of three tests is used to calculate the radioiodination yield of [131I]iodocarvedilol. The radiochemical purity was further confirmed by HPLC analysis, where the retention time of free iodide and [131I]iodocarvedilol were 5 and 11 min, respectively, as shown in the chromatogram (Fig. 3). The UV chromatogram shows a peak at 10.9, which corresponds to cold iodocarvedilol, which coincides with the [131I]iodocarvedilol that appeared nearly at the same retention time in the radio-chromatogram.

Fig. 3
figure 3

HPLC chromatogram for [131I]iodocarvedilol

Effect of reaction time

The yield of labelling is highly influenced by reaction time, which might range from 5 to 120 min. Figure 4 shows that increasing the reaction time from 5 to 30 min increases the yield significantly. The radiochemical yield is unaffected by increasing the reaction time beyond 30 min. The maximal radiochemical yield (92.6 ± 2.77%) requires a minimum reaction time of 30 min.

Fig. 4
figure 4

Effect of Reaction time on the radiochemical yield of [131I]iodocarvedilol. Reaction conditions: 100 (2.46 × 10− 4 mM) µg carvedilol (50 µl) + 200 µg (8.79 × 10− 4 mM) CAT (20 µl) + 10 µl Na131I for ½ hour at pH 6 and 25 °C; n = 3

Effect of carvedilol amount

Figure 5 shows the relationship between radiochemical yield and carvedilol amount, where the radiochemical yield increased from 82.3 to 92.6% as the amount of carvedilol rose from 10 to 300 µg (2.46 × 10− 5 to 7.38 × 10− 4 mM). Further increases in the amount of carvedilol beyond 100 mg had no effect on the labelling yield, which might be explained by the fact that this concentration of carvedilol (100 µg, 2.46 × 10− 4 mM) is sufficient to capture the full produced iodonium ion, resulting in the highest yield (92.6 ± 2.7%).

Fig. 5
figure 5

Effect of substrate amount on the radiochemical yield of [131I]iodocarvedilol. Reaction conditions: X µg substrate + 200 µg (8.79 × 10− 4 mM) CAT (20 µl) + 10 µl Na131I for ½ hour at pH 6 and 25 °C; n = 3

Effect of CAT concentration

After increasing the amount of CAT from 10 to 300 µg (4.39 × 10− 5 to 1.3 × 10− 3 mM) at pH 6 and a 30 minute reaction time, a high radiochemical yield (92.6 ± 2.7 %) was obtained. The formation of undesired oxidative by-products such chlorination, polymerization, and denaturation of Carvedilol causes a drop in iodination yield when the CAT concentration is increased over 200 µg (8.79 × 10− 4 mM) [25]]. The high reactivity and concentration of CAT [2] may be responsible for the production of these contaminants. As a result, the optimal concentration of CAT is strongly advised in order to avoid the occurrence of by-products and achieve high yield and purity (Fig. 6).

Fig. 6
figure 6

Effect of CAT content on the radiochemical yield of [131I]iodocarvedilol. Reaction conditions: 100 µg (2.46 × 10− 4 mM) substrate (50 µl) + X amounts of CAT + 10 µl Na131I for ½ hour at pH 6, at 25 °C; n = 3

Effect of pH of the reaction mixture

Figure 7 shows the effect of the reaction mixture pH on the radioiodination yield of [131I]iodocarvedilol. The reaction medium’s pH was measured in the range of 3 to 10.

The redox potential of chloramine-T is pH dependent and decreases as the medium’s pH rises [26], implying that the type of active oxidizing species of CAT is influenced by the medium’s pH and reaction conditions. When chloramine-T is dissolved in water, it breaks down to ArSO2NCl, which is hydrolyzed in an acidic medium to produce HOCl. The hypohalous acid is hydrolyzed further to produce H2OCl+.

HOCl and H2OCl+ are probable oxidizing species in acidified CAT solutions, while HOCl and ClO are possible oxidizing species in alkaline CAT solutions.

Under acidic circumstances, the produced HOCl or H2OCl+ oxidized the iodine to the oxidative state I+ (iodonium) [27], which quickly reacts with any sites within carvedilol that can undergo electrophilic substitution reactions [26, 28, 29]. Due to the maximal action of CAT at almost neutral pH, the remarkable stability of the carvedilol structure, and the good protonation of the aromatic ring at this pH value, the yield was maximized (92.6 ± 2.77%), yielding H+, which was substituted by the active iodonium ion I+. The yield dropped dramatically when the pH of the reaction medium was changed to the high acidic side, reaching 82.3% at pH 3. Also, the yield was quite low on the alkaline side, reaching 45.4 and 38.3% at pH 8 and 10, respectively. The synthesis of hypoiodite ion (IO) and iodate (IO3) [30], which are not appropriate forms for radioiodination of carvedilol, could explain the decrease in radiochemical yield at alkaline pH.

Fig. 7
figure 7

Effect of pH on the radiochemical yield of [131I]iodocarvedilol. Reaction conditions: 100 µg (2.46 × 10− 4 mM) carvedilol (50 µl) + 200 µg (8.79 × 10− 4 mM) CAT (20 µl) + 10 µl Na131I for ½ hour at different pH, at 25 °C; n = 3

Stability test

Due to the decomposition of the [131I]iodocarvedilol, incubation of the preparation containing [131I]iodocarvedilol for 24 hours at 37 oC resulted in a small decrease in the yield of [131I]iodocarvedilol (92.6 ± 2.77%) and the release of radioactivity from the [131I]iodocarvedilol was 5.9 ± 1.1%, as determined by ITLC (Table 1).

Table 1 In-vitro stability of [131I]iodocarvedilol

In-vivo studies of [131I]iodocarvedilol

In compliance with the guidelines set out by the Egyptian Atomic Energy Authority, the animal Ethics Committee, Labeled Compounds Department, and the protocol approval of Research Ethics Committee in the Faculty of Pharmacy, Cairo University (REC-FOPCU), Egypt, the biodistribution studies were performed.

Table 2 shows the results, which are expressed as percent dose per gram of tissue of [131I]iodocarvedilol. The biological distribution of [131I]iodocarvedilol in rats revealed that it had a great myocardial uptake, good heart persistence, and minimal uptake in the liver, lungs and blood. It was quickly removed from non-target tissues. Both kidneys and liver were the primary excretion organs pathway. The ratio of heart to liver uptake was high (1.922, 3.94, 7.84, 7.84 and 7.53 at 5- 30-, 60-and 120-minute post-injection, respectively) (Fig. 8). The liver activity of [131I]iodocarvedilol was significantly decreased within the first hour compared with 99mTc-Sestamibi activity which declined more slowly over time.

The target-to-non-target ratios of 99mTc-sestamibi, a relatively successful myocardial imaging agent, are also presented in Table 3 [31] for comparison with [131I]iodocarvedilol.

[131I]iodocarvedilol had comparable heart to blood and heart to lung uptake ratios, but a significantly greater heart to liver uptake ratio, which is encouraging us to afford a novel myocardial imaging agent to get high-resolution scintigraphic images after using iodine-123 instead of iodine-131 (the same chemical properties).

Table 2 Biodistribution of [131I]iodocarvedilol in normal rats
Fig. 8
figure 8

The ratio of heart to liver uptake ratio of [131I]iodocarvedilol with time

Table 3 The ratios of target to non-target for [131I]iodocarvedilol and99mTc-sestamibi in rats (n = 3)


In conclusion, using chloramine-T as an oxidizing agent, carvedilol was radiolabeled with NCA 131I by direct electrophilic substitution reaction with a high radiolabeling yield of 92.6 ± 2.77%. In rats, [131I]iodocarvedilol showed the right characteristics for use in cardiac imaging. It has a high heart uptake and heart to liver ratio, both of which are beneficial for high-quality SPECT myocardial imaging. [131I]iodocarvedilol solve most the drawbacks of the FDA approved 99mTc-sestamibi.

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.



Coronary artery disease




Food and Drug Administration


High-performance liquid chromatography


Injected dose


Myocardial perfusion imaging


Sodium-potassium adenosine triphosphatase




Post injection


Single-Photon Emission Computerized Tomography


Target-to-background ratio


Thin Layer Chromatography


  1. Hung G-U. Diagnosing CAD: additional markers from myocardial perfusion SPECT. J Biomedical Res. 2013;27(6):467.

    Article  Google Scholar 

  2. Abd El-Karim SS, et al. Rational design and synthesis of new tetralin-sulfonamide derivatives as potent anti-diabetics and DPP-4 inhibitors: 2D & 3D QSAR, in vivo radiolabeling and bio distribution studies. Bioorg Chem. 2018;81:481–93.

    Article  CAS  PubMed  Google Scholar 

  3. Beller GA, Zaret BL. Contributions of nuclear cardiology to diagnosis and prognosis of patients with coronary artery disease. Circulation. 2000;101(12):1465–78.

    Article  CAS  PubMed  Google Scholar 

  4. Jain D. Technetium-99m labeled myocardial perfusion imaging agents. In seminars in nuclear medicine. Elsevier; 1999.

  5. Husain SS. Myocardial perfusion imaging protocols: is there an ideal protocol? J Nucl Med Technol. 2007;35(1):3–9.

    PubMed  Google Scholar 

  6. Bu L, et al. Evaluation of 99 mTcN-MPO as a new myocardial perfusion imaging agent in normal dogs and in an acute myocardial infarction canine model: comparison with 99 mTc-sestamibi. Mol imaging biology. 2011;13(1):121–7.

    Article  Google Scholar 

  7. Carlin RD, Jan K-m. Mechanism of thallium extraction in pump perfused canine hearts. J Nuclear Medicine: Official Publication Soc Nuclear Med. 1985;26(2):165–9.

    CAS  Google Scholar 

  8. Ziessman HA, O’Malley JP, Thrall JH. Nuclear medicine: the requisites e-book. Elsevier Health Sciences; 2013.

  9. Grunwald AM, et al. Myocardial thallium-201 kinetics in normal and ischemic myocardium. Circulation. 1981;64(3):610–8.

    Article  CAS  PubMed  Google Scholar 

  10. Motaleb M, Moustapha M, Ibrahim I. Synthesis and biological evaluation of 125 I-nebivolol as a potential cardioselective agent for imaging β 1-adrenoceptors. J Radioanal Nucl Chem. 2011;289(1):239–45.

    Article  CAS  Google Scholar 

  11. Verberne HJ, et al. EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT: 2015 revision. Eur J Nucl Med Mol Imaging. 2015;42(12):1929–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schwaiger M. Myocardial perfusion imaging with PET. J Nucl Med. 1994;35(4):693–8.

    CAS  PubMed  Google Scholar 

  13. Llaurado JG. The quest for the perfect myocardial perfusion indicator… still a long way to go. J Nucl Med. 2001;42(2):282–4.

    CAS  PubMed  Google Scholar 

  14. Kailasnath P, Sinusas AJ. Comparison of Tl-201 with Tc-99m-labeled myocardial perfusion agents: technical, physiologic, and clinical issues. J Nuclear Cardiol. 2001;8(4):482–98.

    Article  CAS  Google Scholar 

  15. Banerjee S, Pillai MRA, Ramamoorthy N. Evolution of Tc-99m in diagnostic radiopharmaceuticals. In seminars in nuclear medicine. Elsevier; 2001.

  16. Liu S. Ether and crown ether-containing cationic 99m Tc complexes useful as radiopharmaceuticals for heart imaging.Dalton Transactions, 2007(12): p.1183–1193.

  17. Sakr T, Moustapha M, Motaleb M. 99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessment. J Radioanal Nucl Chem. 2013;295(2):1511–6.

    Article  CAS  Google Scholar 

  18. Schwarz ER, et al. Carvedilol improves myocardial contractility compared with metoprolol in patients with chronic hibernating myocardium after revascularization. J Cardiovasc Pharmacol Therap. 2005;10(3):181–90.

    Article  CAS  Google Scholar 

  19. Ozaydin M, et al. Nebivolol versus carvedilol or metoprolol in patients presenting with acute myocardial infarction complicated by left ventricular dysfunction. Med Principles Pract. 2016;25(4):316–22.

    Article  Google Scholar 

  20. Motaleb M, et al. Radioiodinated paroxetine, a novel potential radiopharmaceutical for lung perfusion scan. J Radioanal Nucl Chem. 2012;292(2):629–35.

    Article  CAS  Google Scholar 

  21. Rashed H, et al. Preparation of radioiodinated ritodrine as a potential agent for lung imaging. J Radioanal Nucl Chem. 2014;300(3):1227–33.

    Article  CAS  Google Scholar 

  22. Selim AA, Motaleb M, Fayez HA. Lung Cancer-Targeted [131I]-Iodoshikonin as Theranostic Agent: Radiolabeling, In Vivo Pharmacokinetics and Biodistribution Pharmaceutical Chemistry Journal, 2022. 55(11): p. 1163–1168.

  23. Motaleb M, et al. An easy and effective method for synthesis and radiolabelling of risedronate as a model for bone imaging. J Label Compd Radiopharm. 2016;59(4):157–63.

    Article  CAS  Google Scholar 

  24. Ebrahem EM, et al. Histopathology, pharmacokinetics and estimation of interleukin-6 levels of Moringa oleifera leaves extract-functionalized selenium nanoparticles against rats induced hepatocellular carcinoma. Cancer Nanotechnol. 2022;13(1):1–26.

    Article  Google Scholar 

  25. Motaleb M, et al. Novel radioiodinated sibutramine and fluoxetine as models for brain imaging. J Radioanal Nucl Chem. 2011;289(3):915–21.

    Article  CAS  Google Scholar 

  26. Sukhdev A, Shubha J. Kinetics and reactivities of ruthenium (III)-and osmium (VIII)-catalyzed oxidation of ornidazole with chloramine-T in acid and alkaline media: a mechanistic approach. J Mol Catal A: Chem. 2009;310(1–2):24–33.

    Google Scholar 

  27. Selim AA, et al. Extraction, purification and radioiodination of Khellin as cancer theranostic agent. Appl Radiat Isot. 2021;178:109970.

    Article  CAS  PubMed  Google Scholar 

  28. Swamy P, Vaz N. Ruthenium (III)-and osmium (VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acid and alkaline media: a kinetic and mechanistic study. Transition Met Chem. 2003;28(4):409–17.

    Article  CAS  Google Scholar 

  29. Jagadeesh R. Os (VIII)-catalyzed and uncatalyzed oxidation of biotin by chloramine-T in alkaline medium: comparative mechanistic aspects and kinetic modeling. J Mol Catal A: Chem. 2007;265(1–2):70–9.

    Google Scholar 

  30. Ibrahim A, et al. Radioiodinated anastrozole and epirubicin as potential targeting radiopharmaceuticals for solid tumor imaging. J Radioanal Nucl Chem. 2015;303(1):967–75.

    Article  CAS  Google Scholar 

  31. Chu J, et al. [99m TcN (PNP5)(NOEt)]+: a novel potential myocardial perfusion imaging agent. J Radioanal Nucl Chem. 2006;269(1):175–9.

    Article  CAS  Google Scholar 

Download references


Not applicable.


No funding.

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Author information

Authors and Affiliations



MAM, KMA, HAS and ITI design the work and perform all experimental steps equally. All authors read and approved the final manuscript.

Corresponding author

Correspondence to M. A. Motaleb.

Ethics declarations

Ethics approval and consent to participate

In compliance with the guidelines set out by the Egyptian Atomic Energy Authority, the animal Ethics Committee, Labeled Compounds Department, and the protocol approval of Research Ethics Committee in the Faculty of Pharmacy, Cairo University (REC-FOPCU), Egypt, the biodistribution studies were performed. This study was conducted in accordance with the ARRIVE guidelines (

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Motaleb, M.A., Attalah, K.M., Shweeta, H.A. et al. Synthesis and biological evaluation of [131I]iodocarvedilol as a potential radiopharmaceutical for heart imaging. BMC Chemistry 17, 21 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: