• Nuclear Engineering and Technology
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• v.54 no.6
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• pp.2204-2212
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• 2022

Recently, the demand for alpha imaging detectors for quantifying the distributions of alpha particles has increased in various fields. This study aims to reconstruct a high-resolution image from an alpha imaging detector by applying a super-spatial resolution method combined with the maximum-likelihood expectation maximization (MLEM) algorithm. To perform the super-spatial resolution method, several images are acquired while slightly moving the detector to predefined positions. Then, a forward model for imaging is established by the system matrix containing the mechanical shifts, subsampling, and measured point-spread function of the imaging system. Using the measured images and system matrix, the MLEM algorithm is implemented, which converges towards a high-resolution image. We evaluated the performance of the proposed method through the Monte Carlo simulations and phantom experiments. The results showed that the super-spatial resolution method was successfully applied to the alpha imaging detector. The spatial resolution of the resultant image was improved by approximately 12% using four images. Overall, the study's outcomes demonstrate the feasibility of the super-spatial resolution method for the alpha imaging detector. Possible applications of the proposed method include high-resolution imaging for alpha particles of in vitro sliced tissue and pre-clinical biologic assessments for targeted alpha therapy.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.10 no.1
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• pp.33-41
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• 2024

Targeted alpha therapy (TAT) harnesses the potent cytotoxicity of alpha particles emitted by radioisotopes to selectively eradicate cancer cells while minimizing damage to surrounding healthy tissues. Developing radiopharmaceutical for TAT, alpha particle imaging devices are used to identify distribution and behavior of the radiopharmaceutical in body, to evaluate efficacy and safety of the radiopharmaceutical. This paper explores the challenges and advancements in alpha particle imaging devices for TAT. Researchers are turning to innovative alpha particle imaging devices capable of directly detecting alpha particles to achieve higher spatial resolution and accuracy in mapping radioisotope distribution within organs. This review surveys the landscape of alpha particle imaging devices developed worldwide, including scintillator based-, semiconductor based-, and gas detector based systems. Their underlying principles, unique features, and strategies for enhancing performance are examined. By shedding light on the state-of-the-art technologies supporting advancements in TAT research, this review aims to introduce the ongoing efforts to refine the vision on biodistribution of radiopharmaceuticals for TAT.

• Bulletin of the Korean Chemical Society
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• v.29 no.6
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• pp.1107-1114
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• 2008

It is important to identify selective ligands for the estrogen receptor subtypes ER$\alpha$ or ER$\beta$ to evaluate them as pharmaceutical targets in breast cancer. To develop ER$\beta$-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ER$\alpha$ vs ER$\beta$. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ER$\beta$/ER$\alpha$ selectivity, respectively. However, their binding affinities to ER$\alpha$ and ER$\beta$ were very low.

• Journal of Biomedical Engineering Research
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• v.26 no.4
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• pp.223-230
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• 2005

This paper presents a new approach to investigate spatial correlation between independent components of brain alpha activity in functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). To avoid potential problems of simultaneous fMRI and EEG acquisitions in imaging pure alpha activity, data from each modality were acquired separately under a 'three conditions' setup where one of the conditions involved closing eyes and relaxing, thus making it conducive to generation of alpha activity. The other two conditions -- eyes open in a lighted room or engaged in a mental arithmetic task, were designed to attenuate alpha activity. Using a Mixture Density Independent Component Analysis (MD-ICA) that incorporates flexible non-linearity functions into the conventional ICA framework, we could identify the spatiotemporal components of fMRI activations and EEG activities associated with the alpha rhythm. Then, the sources of the individual EEG alpha activity component were localized by a Maximum Entropy (ME) method that is specially designed to find the most probable dipole distribution minimizing the localization error in sense of LMSE. The resulting active dipoles were spatially transformed to 3D MRls of the subject and compared to fMRI alpha activity maps. A good spatial correlation was found in the spatial distribution of alpha sources derived independently from fMRI and EEG, suggesting the proposed method can localize the cortical areas responsible for generating alpha activity successfully in either fMRI or EEG. Finally a functional connectivity analysis was applied to show that alpha activity sources of both modalities were also functionally connected to each other, implying that they are involved in performing a common function: 'the generation of alpha rhythms'.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.4
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• pp.171-175
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• 2015

Objectives: The objective of this study was to identify salivary and serum concentrations of interleukin (IL)-8, IL-6, and tumor necrosis factor alpha ($TNF-{\alpha}$) in patients with oral lichen planus, oral leukoplakia, oral submucous fibrosis, and healthy controls. Materials and Methods: Patients selected included 54 oral lichen planus (41 to 65 years), 50 oral leukoplakia (42 to 65 years), 51 oral submucous fibrosis (41 to 65 years), and 50 healthy controls (42 to 65 years). Oral lichen planus, oral leukoplakia, and oral submucous fibrosis cases were diagnosed using histopathological analysis. Salivary and serum cytokine concentrations were measured using enzyme-linked immunoassay kits in all subjects. Results: The levels of serum and salivary $TNF-{\alpha}$, IL-6, and IL-8 were statistically significantly increased in oral leukoplakia, submucous fibrosis, and lichen planus in contrast to normal healthy subjects (P<0.05). Serum and salivary correlation analysis revealed strong and highly significant correlations for $TNF-{\alpha}$, IL-6, and IL-8 in all groups (r=0.72-0.82, P<0.05). Conclusion: Salivary and serum cytokines were also elevated when analyzed in oral precancerous lesions. Thus, salivary and serum IL-8, IL-6, and TNF-${\alpha}$ levels might act as diagnostic markers for detection of oral precancer.

• 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.9 no.2
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• pp.93-99
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• 2023

Malignant melanoma is a very aggressive metastatic skin cancer with a high mortality rate. Thus, an accurate early diagnosis of metastatic melanoma is the best treatment for patients. The melanocortin-1 receptor (MC1R) is overexpressed in human melanoma cells but exhibits low expression in normal tissues. This characteristic makes it an attractive target for detection of malignant melanoma. Alpha-melanocyte stimulating hormone (α-MSH), one of the endogenous ligands of MC1R, binds to MC1R through its core sequence. However, it is challenging to utilize the native structure of α-MSH, so researchers have found that stabilizing it through cyclization can offer more favorable outcomes in both preclinical and clinical studies. This review introduces the development of radionuclide-labeled α-MSH derivatives that selectively bind to MC1R, a malignant melanoma-specific target. It also explains on the development of cyclized α-MSH derivatives and the results of biological evaluations related to renal uptake.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.108-112
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• 2016

Molecular imaging with the radiolabeled RGD peptides for ${\alpha}_v{\beta}_3$ integrin has been an increasing interest for tumor diagnosis and the treatment monitoring. Recently, $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ was developed for quantification of ${\alpha}_v{\beta}_3$ integrin and its biological properties was elucidated. To better understand the molecular process in vivo, we performed the kinetic analysis for the $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$. After preparation of a radiotracer, dynamic PET images were obtained in the U87MG xenograft mice for 60 min (n = 6). Binding potential values were estimated from the 3-tissue compartment model, reference Logan and simplified reference tissue model. In the early time frame (0-20 min), the liver, kidney, intestine, urinary bladder and tumor were visualized but these uptakes were diminished as time went by. The tumors showed a good contrast at 40 min after administration. $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ showed the 2-fold uptake in the tumor compared with that in the muscle. The parametric maps for binding values also provide the higher tumor-to-background contrast than the static images. A binding value obtained from the 3-tissue compartment model was comparable to other modeling methods. From these results, we conclude that $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ may be a promising PET radiotracer for the evaluation of angiogenesis.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.1
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• pp.1-8
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• 2007

This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of $^{213}Bi$, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.171-174
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• 2004

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.