• Korean Journal of Clinical Laboratory Science
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• v.56 no.1
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• pp.43-51
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• 2024

[⁶⁸Ga]Ga-FAPI-04 is a promising radiopharmaceutical that binds specifically to fibroblast activation protein, which is overexpressed in more than 90% of malignant epithelial tumors but not in normal healthy tissue. This study aimed to develop an efficient method for producing ⁶⁸Ga-labelled FAPI-04 using a cassette-based automated synthesizer. [⁶⁸Ga]GaCl₃ was eluted from an Eckert & Ziegler Medical germanium-68/gallium-68 generator using 2.5 mL of 0.1 M HCl. The synthesis of the [⁶⁸Ga]Ga-FAPI-04 was performed using different concentrations of HEPES (1~2.5 M; 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) in 3~10 minutes; amounts of FAPI-04 precursor (5~50 ㎍) and reaction temperature (25℃~100℃) were optimized on the BIKBox^® synthesizer. The labeling efficiency of [⁶⁸Ga]Ga-FAPI-04 was greater than 96% (decay corrected) using 25 ㎍ FAPI-04 synthesized in 10 minutes at 100℃ in 2 M HEPES (pH 3.85), and its stability was greater than 99% at 6 hours. The total synthesis time of [⁶⁸Ga]Ga-FAPI-04 was 32.4 minutes, and the product met all quality control criteria. In this study, we developed and optimized a labeling method using [⁶⁸Ga]Ga-FAPI-04 using a cassette-based synthesizer. The devised method is expected to be useful for supplying [⁶⁸Ga]Ga-FAPI-04 for diagnosis in clinical practice.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.330-336
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• 2009

Purpose: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide $^{68}$Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Materials and Methods: Various concentrations of NOTA 3HCl and DOTA 4HCl were labeled with 1 mL $^{68}$GaCl$_3$ (0.18$\sim$5.75 mCi in 0.1 M HCl in various pH. NOTA 3HCl (0.373 mM) was labeled with $^{68}$GaCl$_3$(0.183$\sim$0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$, GaCl$_3$, MgCl$_2$ or CaCl$_2$ (0$\sim$6.07 mM) at room temperature. The labeling efficiencies of $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. Results: $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37$^{\circ}C$. NOTA was labeled at room temperature while DOTA required heating for labeling. $^{68}$Ga-NOTA labeling efficiency was reduced by CuCl$_2$, FeCl$_2$, InCl$_2$, FeCl$_3$ or CaCl$_3$, however, was not influenced by MgCl$_2$ or CaCl$_2$. The protein binding was low (2.04$\sim$3.32%). Log P value of $^{68}$Ga-NOTA was -3.07 indicating high hydrophilicity. Conclusion: We found that NOTA is a better bifunctional chelating agent than DOTA for $^{68}$Ga labeling. Although, $^{68}$Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.253-260
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• 2023

The germanium-68/gallium-68 (⁶⁸Ge/⁶⁸Ga) generator has high spatial utilization and requires little maintenance, making it economical and easy to produce. Thus, the frequency of use of ⁶⁸Ga radiopharmaceuticals is rapidly increasing worldwide. Therefore, this study attempted to develop an automated synthesizer for the routine clinical application of ⁶⁸Ga radiopharmaceuticals. The automated synthesizer was based on a fixed tubing system and the structure was designed after adjusting the position of the parts to reflect the synthesis method. Using various components that can be supplied in Korea, the automated synthesizer was manufactured at a much lower price cost than that of a commercialized automated synthesizer sold by companies. ⁶⁸Ga-DOTA-[Tyr3]-octreotide (⁶⁸Ga-DOTATOC) was synthesized to evaluate the performance of the automated synthesizer. ⁶⁸Ga-DOTATOC could be synthesized with about 65% of non-decay corrected yield, and the synthesized ⁶⁸Ga-DOTATOC met all quality control standards. We have synthesized ⁶⁸Ga-DOTATOC more than 100 times, and only faced a few problems caused by mechanical errors. In this study, we successfully developed a simple automated synthesizer for ⁶⁸Ga radiopharmaceuticals with high reproducibility. As various ⁶⁸Ga radiopharmaceuticals have recently been developed, it is expected that the automated synthesizer developed in this study will be useful for routine clinical use.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.1
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• pp.22-36
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• 2016

$^{68}Ga$ is a promising radionuclide for positron emission tomography (PET). It is a generator-produced ($^{68}Ge/^{68}Ga$-generator) radionuclide with a half-life of 68 min. The employment of $^{68}Ga$ for basic research and clinical applications is growing exponentially. Bifunctional chelators (BFCs) that can be efficiently radiolabeled with $^{68}Ga$ to yield complexes with good in vivo stability are needed. Given the practical advantages of $^{68}Ga$ in PET applications, gallium complexes are gaining increasing attention in biomedical imaging. However, new $^{68}Ga$-labeled radiopharmaceuticals that can replace $^{18}F$-labeled agents like [$^{18}F$]fluorodeoxyglucose (FDG) are needed. The majority of $^{68}Ga$-labeled derivatives currently in use consist of peptide agents, but the development of other agents, such as amino acid or nitroimidazole derivatives and glycosylated human serum albumin, is being actively pursued in many laboratories. Thus, the availability of new $^{68}Ga$-labeled radiopharmaceuticals with high impact is expected in the near future. Here, we present an overview of the different new classes of chelators for application in molecular imaging using $^{68}Ga$ PET.

• Progress in Medical Physics
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• v.22 no.4
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• pp.172-177
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• 2011

The purpose of this study was to analyze $^{68}Ga$-BAPEN dynamic PET image in rat myocardium to evaluate potential of this radiotracer as a perfusion imaging agent. Animal PET/CT scan was done in 9 rats during 120 minutes. Especially we synthesized $^{68}Ga$-BAPEN with kit which is simple and low cost method. PET images showed the in vivo dynamic distribution of $^{68}Ga$-BAPEN in the chest region of rats. Initially $^{68}Ga$-BAPEN PET images showed aorta and liver activities and a few minutes later, $^{68}Ga$-BAPEN moved to myocardium. Regions of interest were drawn on myocardium, liver, lung and blood pool. Time-activity curves showed significant uptake of $^{68}Ga$-BAPEN in myocardium. The contrast ratios of myocardial to blood pool, lung and liver at 60 minutes after injection were 1.66, 2.82 and 0.60. To estimate accurate kinetic parameters, 60 minutes after injection was required to PET scan as myocardium image contrast ratios reached to constant values. As a result, $^{68}Ga$-BAPEN would be suitable radiotracer for PET which can applied to diagnosis of myocardial perfusion diseases after further preclinical and clinical investigations.

• Journal of radiological science and technology
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• v.41 no.4
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• pp.321-327
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• 2018

The purpose of this study is to compare PET imaging performance with Fluorine-18 ($^{18}F$) and Gallium-68 ($^{68}Ga$) for influence of physical properties of PET tracer. Measurement were performed on a Siemens Biograph mCT64 PET/CT scanner using NEMA IEC body phantom and Flangeless Esser PET phantom containing filled with $^{18}F$ and $^{68}Ga$. Emission scan duration(ESD) was set to 1, 2, 3, 4 and 5min/bed for $^{68}Ga$ and 1min/bed for $^{18}F$. The PET image were evaluated in terms of contrast, spatial resolution. Under same condition, The percentage of contrast recovery measured in the phantom ranged from 16.88% to 72.56% for $^{68}Ga$ and from 27.51% to 74.43% for $^{18}F$ and The FWHM value to evaluate spatial resolution was 10.96 mm for $^{68}Ga$ and 9.19 mm for $^{18}F$. For this study, $^{18}F$ produces better image contrast and spatial resolution than $^{68}Ga$ due to higher positron yield and lower positron energy ($^{18}F$: 96.86%, 633.5 keV, $^{68}Ga$: 88.9%, 1899 keV), The physical properties of PET tracer effect on the PET image. $^{68}Ga$ image applying ESD of 3, 4, 5min/bed were showed similar to $^{18}F$ image with ESD of 1min/bed. This study suggests that increasing ESD for acquiring $^{68}Ga$ PET image seem to be similar to $^{18}F$ image.

• Journal of Radiation Industry
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• v.10 no.4
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• pp.189-192
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• 2016

$^{68}Ga$ has emerged as a promising candidate for non-invasive diagnostic imaging within Positron Emission Tomography (PET) because of its advantageous radiochemical characteristics ($t_{1/2}=68min$, ${\beta}^+$ yield ~89%). $^{68}Ga$ forms a stable chelation with various ligands and it is possible to be quickly and easily study using a $^{68}Ge/^{68}Ga$ generator. Commercial $^{68}Ge/^{68}Ga$ generators are chromatographic system using the inorganic materials such as alumina and tin dioxide which are employed as column matrixes for $^{68}Ge$. In this study, we tried out to make $^{68}Ge/^{68}Ga$ generator system with the $^{68}GeO_2$ microstructures for column matrix. $^{68}Ge$ tends to have stable bond with oxide as $^{68}GeO_2$ microstructures. The $^{68}GeO_2$ has been synthesized by hydrolysis of $GeCl_4$ (sol-gel method) and characterized by X-ray diffraction and scanning electron microscope for geometrical analysis. The stability of $GeO_2$ was tested using eluents with diverse solvents(water, ethanol and 0.1 N HCl). The radioactivity of $^{68}Ga^{3+}$ in eluate through $GeO_2$ was measured to prove a function as column material for a generator.

• Journal of the Korean Society of Radiology
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• v.12 no.1
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• pp.1-7
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• 2018

$^{68}Ga$ was eluted from a $^{68}Ge/^{68}Ga$ radionuclide generator. $^{68}Ga$ decays into $^{68}Zn$, with a half life=67.8min. The decay is 88.9 % by ${\beta}$+ and 11.1 % by EC. The main ${\beta}$+ decay (87.7 %) is to the ground level of $^{68}Zn$ and it is a pure positron emission branch. A small fraction decays ${\beta}$+ (1.2 %) into an excited level of $^{68}Zn$, which promptly decays into the ground level with a ${\gamma}$ (1.077 Mev). This can constitute prompt gamma contamination in the PET data, if the 1.077 Mev ${\gamma}$ has a scatter interaction in the patient, and generates a lower energy ${\gamma}$ in coincidence with the positron annihilation pair. The purpose of this study was to evaluate standardized uptake value(SUV) before and after applying prompt gamma rays correction on $^{68}Ga$-DOTATOC PET/CT image. Fifty patient underwent PET/CT 1 hour after injection of the $^{68}Ga$-DOTATOC. The SUVmax and SUVmean of lesions and normal tissues (Pituitary, Lung, Liver, Spleen, Kidney, Intestine) were evaluated before and after applying prompt gamma correction on $^{68}Ga$-DOTATOC PET/CT image. Additionally, the SUVmax of each lesions and SUVmean of the soft tissues were measured on images. and target to background ratios (TBR) were calculated as quantitative indices. Among 15 patients, 25 of lesions (Pancreas, Liver, Thoracic Spine, Brain) with increased uptake on $^{68}Ga$-DOTATOC PET/CT image. SUVmax and SUVmean were increased in lesion site and normal tissue after prompt gamma rays correction. TBR was $51.51{\pm}49.28$ and $55.50{\pm}53.12$ before and after prompt gamma rays correction, respectively. (p<0.0001)

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.85-90
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• 2017

$^{68}Ga-PET$ is of growing importance in the practice of nuclear medicine diagnostic imaging for neuroendocrine tumors as well as prostate cancers. Following this interests, we herein present the radiosynthesis process of [$^{68}Ga$]edotreotide ([$^{68}Ga$]DOTA-TOC) based on the fully automated procedure for clinical doses that can be provided the reduction of radiation exposure and high reproducibility. The quality controls of clinical doses in compliant with European Pharmacopoeia are also discussed.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.46-52
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• 2015

Herein we present the synthesis of $^{68}Ga$-labeled gold nanoparticles for in vivo PET imaging. A novel chelator DTPA-Cys was easily prepared from diethylenetriaminepentaacetic dianhydride in high yield. The ${\alpha}_v{\beta}_3$ integrin receptor targeted gold nanoparticle probe was synthesized by using DTPA-Cys, polyethylene glycol and cRGD peptide. $^{68}Ga$ labeling of cRGD conjugated gold nanoparticle was carried out at $40^{\circ}C$ for 30 min. Observed radiochemical yield was more than 75% as determined by radio-TLC and the probe was purified by centrifugation. In vitro stability test showed that 90% of $^{68}Ga$-labeled gold nanoparticle probe was stable in FBS for 1 h. Those results demonstrated that $^{68}Ga$-labeled gold nanoparticle could be used as a potentially useful probe for specific tumor imaging.