• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.129-137
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• 2022

Bombesin has a high binding affinity to gastrin-releasing peptide receptor (GRPR) and can be used as a targeting ligand in GRPR-related cancers. Because GRPR is overexpressed in prostate cancer, bombesin analogues have been investigated extensively for diagnosis and treatment of prostate cancer. In nuclear medicine, bombesin derivatives labeled with radiometals such as ^55/57Co, ⁶⁴Cu, ⁶⁸Ga, ^99mTc, and ¹⁷⁷Lu or radiohalogen such as ¹³¹I and ²¹¹At were developed as markers for early detection of tumors and theragnostic tool for cancer treatment. This review focuses on the introduction of bombesin-based radiopharmaceuticals that are studied in pre-clinical or clinical research.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.39-44
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• 2022

The development of methods for the inert and stable radiohalogenation of targeted radiopharmaceuticals is a prerequisite for real-time diagnosis and therapy using radiohalogenated radiopharmaceuticals. Radiohalogenated carboranes demonstrate superior stability in vivo and versatile applications compared with directly labeled tyrosine analogues or synthetically modified organic compounds. Herein, we focus on the most common approaches for the radioiodination (¹²³l, ¹²⁴l, ¹²⁵l, and ¹³¹l) of carborane derivatives.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.71-78
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• 2019

Nuclear imaging is one of the most powerful measures for non-invasive diagnosis of myocardial vascular disease. Radionuclide such as ¹³N, ¹⁵O, ²⁰¹Tl and ⁸²Rb is used for the measurement of cardiac blood flow. ¹³N, ¹⁵O and ²⁰¹Tl are produced in cyclotrons while ⁸²Rb is obtained from generator. Rubidium (Rb), an alkali ion, behaves biologically like potassium, and accumulates in myocardial tissue. Rb has rapid blood clearance profile which allows the use of ⁸²Rb with a short physical half-life of 75 s for non-invasive evaluation of regional myocardial perfusion. There are several advantages of ⁸²Rb over other radioisotopes. An ultra-short half-life significantly reduces the exposure of patients to radiation and allows to repeat injections for studying the effects of medical intervention. As a positron emitter, ⁸²Rb allows positron emission tomography (PET) imaging which have shown superior diagnostic performances. ⁸²Rb can be produced from generator by decay of its parent ⁸²Sr. However, the preparation of ⁸²Sr is difficult, because appropriate purity is required to meet the specification of the product. Recently reported procedure from ARRONAX research institute showed that a Chelex-100 resin is sufficient for this purpose and additional column is not necessary. Whereas Brookhaven National Laboratory (BNL) procedure contains three ion exchange resin separation, including Chelex-100 resin. Currently, since ⁸²Sr production site is non-existent in Korea, Korea Atomic Energy Research Institute (KAERI) has plan to produce ⁸²Sr within specifications. We compared ⁸²Sr purification procedures reported from ARRONAX and BNL to investigate the most suitable procedure for our conditions.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.3-9
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• 2020

Tetraiodothyroacetic acid (tetrac) is a derivative of thyroid hormone T₄ and causes anti-angiogenesis by blocking T₄ binding to integrin α_vβ₃. In this study, we synthesized [^99mTc]Tc-Cys-Asp-Gly(CDG)-tetrac and evaluated it in vitro as a tumor angiogenesis imaging ligand. The CDG was conjugated to tetrac as a chelator for technetium-99m labeling. The cold vial containing CDG-tetrac, sodium glucoheptonate, and reducing agent was completed under nitrogen-filled atmospheric glove bag. [^99mTc]Tc-CDG-tetrac was synthesized in quantitative yield by heating the cold vial with [^99mTc]TcO₄^- at 100℃ for 30 min. In vitro serum stability of [^99mTc]Tc-CDG-tetrac was measured by incubating the radioligand in 50% fetal bovine serum at 37℃ and analyzing the incubation mixture by radio-TLC, which showed high stability over 6 h (≥ 98%). Cell binding study was carried out by incubating [^99mTc]Tc-CDG-tetrac with human umbilical vein endothelial (HUVE) cells at 37℃ for 6 h. The cell binding of the radioligand increased from 100% at 0.5 h to 293.7% at 6 h in a time-dependent manner. For blocking study, the cells were incubated with the radioligand in the presence of either tetrac (20 μM) or cRGDyK (20 μM) at 37℃ for 4 h. The results demonstrated that the cell binding of the radioligand was inhibited by tetrac (19.1%) or cRGDyK (35.6%), indicating specific binding of the radioligand to integrin α_vβ₃. Thus, this study suggests that [^99mTc]Tc-CDG-tetrac may be a potential radioligand for tumor angiogenesis imaging.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.31-37
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• 2015

Chelating agents 1,4,7-triazacyclononanetriacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 30-amino-3,14,25-trihydroxy-3,9,14,20,25-penta-azatriacontane-2,10,13,21,24-pentaone (desferrioxamine, DFO) were labeled with $^{68}Ga$ and tested in vitro properties to check the feasibility of using DFO as a bifunctional chelating agent or renal imaging agent. The chelating agents of concentration $2{\mu}M$ were labeled with $^{68}Ga$ in 0.1 M HCl at pH 1.7-10.3 at room temperature and $80^{\circ}C$ and the optimal pH for labeling each chelating agent was found. And then, the chelating agents were labeled with $^{68}Ga$ in various concentration of chelating agents at optimal pH. The labeled chelating agents were subject to stability test in human serum and to binding studies to human red blood cell (RBC) and plasma protein. The optimal pH's of NOTA, DOTA and DFO for $^{68}Ga$-labeling were 4.4, 3.6 and 5.6, respectively. DFO ($10{\mu}M$) showed high labeling efficiency (>97%) at pH 5.6. All the labeled chelating agents showed high stability in human serum. $^{68}Ga$-DFO showed low RBC binding but significant amount was bound to plasma protein. The results demonstrated that $^{68}Ga$-DFO can be used as a bifunctional chelating agent but not as a renal imaging agent.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.137-144
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• 2015

Hypoxia is an important adverse prognostic factor for tumor progression and is a major cause of failure of radiation therapy. In case of short-term hypoxia, the metabolism can recover to normal, but if hypoxia persists, it causes irreversible cell damage and finally leads to death. So a hypoxia marker would be very useful in oncology. In particular, 2-nitroimidazole can be reduced to form a reactive chemical species, which can bind irreversibly to cell components in the absence of sufficient oxygen, thus, the development of radiolabeled nitroimidazole derivatives for the imaging of hypoxia remains an active field of research to improve cancer therapy result. 2-nitroimidazole based hypoxia marker, [$^{18}F$]FMISO holds promise for the evaluation of tumor hypoxia by Positron emission tomography (PET), at both global and local levels. In the present study, [$^{18}F$]FMISO was synthesized using an automatic synthesis module with high radiochemical purity (>99%) in 60 min. Immunohistochemical analysis using pimonidazole confirmed the presence of hypoxia in xenografted CT-26 tumor tissue. A biodistribution study in CT-26 xenografted mice showed that the increased tumor-to-muscle ratio and tumor-to-blood ratios from 10 to 120 min post-injection. In the PET study, [$^{18}F$]FMISO also showed increased tumor-to-muscle ratios from 10 to 120 min post-injection. In conclusion, this study demonstrates the feasibility and utility of [$^{18}F$]FMISO for imaging hypoxiain mouse colon cancer model using small animal PET.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.104-108
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• 2015

Human serum albumin (HSA) has potential for diagnosis and therapy in clinical setting. The purpose of experiments was to develop and evaluate $^{68}Ga$-HSA as a PET agent for diagnosis of acute inflammation. NOTA-HSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to HSA in 0.1 M sodium carbonate buffer (pH 9.5) and then purified using a PD-10 size-exclusion column. NOTA-HSA was labeled with $^{68}Ga$ at room temperature for 10 min, and 8.4% sodium hydrogen carbonate buffer was added for neutralization. $^{68}Ga$-NOTA-HSA was purified using alumina N plus light cartridge and $0.22{\mu}m$ syringe filter. Labeling efficiency and radiochemical purity were determined by ITLC-SG with 0.1 M citric acid. Biodistribution study was performed in a male BALB/c mice model of Carrageenan-induced acute inflammation. Animal PET study was performed in acute inflammation mice model after tail vein injection of $^{68}Ga$-HSA. This radiotracer showed high labeling efficiency (>99%) around pH 7. Biodistribution study showed higher inflamed footpad uptake than control footpad uptake. Animal PET study revealed 2 times higher uptake on inflamed footpad compared to control footpad. In these experiments, we developed $^{68}Ga$-HSA for acute inflammation PET imaging and evaluated it in a mouse disease model. The results demonstrated that $^{68}Ga$-HSA has potential as a PET imaging agent for diagnosis of acute inflammation.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.1
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• pp.54-60
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• 2019

Sentinel lymph node (SLN) imaging plays an important role in surgery of patients with breast cancer and melanoma. In this study, avidin (Av), a tetrameric protein glycosylated with mannose and N-acetylglucosamine molecules, was labeled with $^{64}Cu$ and then evaluated for LN imaging. $^{64}Cu$-Labeled $NeutrAvidin^{TM}$ (NAv), a non-glycosylated form of Av, was used for comparison. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-conjugated Av and NAv were prepared from the corresponding proteins and DOTA-NHS ester, which were then labeled with copper-64 and purified using PD-10 columns. The numbers of DOTA molecules conjugated to Av and NAv were 4.9 and 3.3, respectively. [$^{64}Cu$]Cu-DOTA-conjugated Av and NAv were prepared in 93% and 73% radiochemical yields, respectively. In vitro serum stability study showed that copper-64 remained stable on all radiotracers for 24 h (>97%). MicroPET/CT images showed that high radioactivity was accumulated in LNs within 15 min after footpad-injection of radiotracers. Tissue distribution data of mice demonstrated significantly higher uptake in the popliteal (PO) LN than lumbar (LU) LN for $^{64}Cu$-labeled Av (relative % ID/g excluding the injection sites: 66.2% and 26.0%, respectively) compared with those of $^{64}Cu$-labeled NAv (43.0% and 49.2%, respectively). The results of this study suggest that mannose molecules on Av enabled the radiotracer to retain in the first LN after mouse footpad-injection.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.2
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• pp.57-64
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• 2018

${\omega}-[^{18}F]$-Fluorohexadecanoic acid (FHA) has been used for imaging of fatty acid metabolism of myocardium. To increase retention of radiolabeled fatty acid by blocking ${\beta}$-oxidation, methyl branched analogues have been used. In this experiment, we tried to synthesize 18F-labeled ${\alpha}-$, ${\beta}-$ and ${\omega}-FHA$ for imaging of the myocardial fatty acid metabolism. We synthesized ${\alpha}-$, ${\beta}-$ and ${\omega}$-mesylated methyl hexadecanoates and labeled with $^{18}F$ by reacting with $[^{18}F]$TBAF in acetonitrile at $80^{\circ}C$ for 10 min. Methyl ester group was removed by 1 M NaOH at $80^{\circ}C$ for 5 min. The yields of ${\alpha}-[^{18}F]$ and ${\omega}-[^{18}F]FHA$ were 25.5 and 45.5%, respectively [EOS]. However, ${\beta}-[^{18}F]FHA$ was not labeled at all due to a fast elimination reaction. The biodistribution study in ICR-mice showed that ${\omega}-[^{18}F]FHA$ has higher myocardial uptake and lower liver uptake than ${\alpha}-[^{18}F]FHA$. The electron-withdrawing effect of fluorine at ${\alpha}-$ position is believed to be the major factor affecting the biodistribution.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.147-152
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• 2021

C-11 Radiolabeled amino acid-based radiopharmaceuticals such as [¹¹C]MET for brain tumor PET imaging have limitations due to their short half-life (20 min). F-18 radiolabeled amino acid derivatives have been developed to overcome for the short half-life, one of which is [¹⁸F]FET. Brain tumor imaging using [¹⁸F]FET showed high uptake in tumor region and no non-specific uptake in inflammatory tissue, which was useful in discriminating the difference between inflammation and tumor especially. In this study, [¹⁸F]FET was synthesized using an automatic synthesis module and quality tests were carried out including enantiomeric purity analysis with reference compounds. Radiochemical yield was 50.3 ± 4.9% (n=7, decay-corrected) with molar activity of 76 ± 17 GBq/mmol. The radiochemical purity of >99%. Enantiomeric purity of [¹⁸F]FET using chiral HPLC analysis showed >99%, which was confirmed by co-injection with the L-FET and D-FET authentic standards. [¹⁸F]FET was prepared with high radiochemical yield and molar activity including no racemate mixture.