• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.49-55
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• 2023

Tumors are encircled by various non-cancerous cell types in the extracellular matrix, including fibroblasts, endothelial cells, immune cells, and cytokines. Fibroblasts are the most critical cells in the tumor stroma and play an important role in tumor development, which has been highlighted in some epithelial cancers. Many studies have shown a tight connection between cancerous cells and fibroblasts in the last decade. Regulatory factors secreted into the tumor environment by special fibroblast cells, cancer-associated fibroblasts (CAFs), play an important role in tumor and vessel development, metastasis, and therapy resistance. This review addresses the development of FAP inhibitors, emphasizing the first, second, and latest generations. First-generation inhibitors exhibit low selectivity and chemical stability, encouraging researchers to develop new scaffolds based on preclinical and clinical data. Second-generation enzymes such as UAMC-1110 demonstrated enhanced FAP binding and better selectivity. Targeted treatment and diagnostic imaging have become possible by further developing radionuclide-labeled fibroblast activation protein inhibitors (FAPIs). Although all three FAPIs (01, 02, and 04) showed excellent preclinical and clinical findings. The final optimization of these FAPI scaffolds resulted in FAPI-46 with the highest tumor-to-background ratio and better binding affinity.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.23-30
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• 2015

Radioisotopes emitting low-range highly ionizing radiation such as ${\beta}$-particles are of increasing significance in internal radiotherapy. Among the ${\beta}$-particle emitting radioisotopes, $^{67}Cu$ is an attractive radioisotope for various nuclear medicine applications due to its medium energy ${\beta}$-particle, gamma emissions, and 61.83-hour half-life, which can also be used with $^{64}Cu$ for PET imaging. The production and application of the ${\beta}$-emitting radioisotope $^{67}Cu$ for therapeutic radiopharmaceutical are outlined, and different production routes are discussed. A survey of copper chelators used for antibody labeling is provided. It has been produced via proton, alpha, neutron, and gamma irradiations followed by solvent extraction, ion exchange, electrodeposition. Clinical studies using $^{67}Cu$-labelled antibodies in lymphoma, colon carcinoma and bladder cancer patients are reviewed. Widespread use of this isotope for clinical studies and preliminary treatments has been limited by unreliable supplies, cost, and difficulty in obtaining therapeutic quantities.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.129-134
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• 2019

Over a few decades, copper radioisotopes and their chelation chemistry for radiopharmaceuticals have played crucial role in the radiopharmaceutical science area. A variety of chelators have been required for their stable targeting ability in physiological conditions. For radiolabeling with copper-64 into biomolecules, thermodynamic stability, kinetic inertness, pH stability, and redox stability should be considered. In this regard, many researchers have attempted to develop the chelators that can bind with copper more tightly, rapidly and stably for copper radiolabeling. This review discusses the chemistry of copper, its suitable chelators and characteristics, while elucidating the evaluations of each chelator for radiolabeling.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.2
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• pp.139-145
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• 2020

Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.112-117
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• 2007

Imaging distribution of ${\beta}-amyloid$ plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the ${\beta}-amyloid$ plaques includes using radiolabeled peptides which can be only applied for peripheral ${\beta}-amyloid$ plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging ${\beta}-amyloid$ plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for ${\beta}-amyloid$ imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for ${\beta}-amyloid$ imaging agent.

• Journal of the Optical Society of Korea
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• v.14 no.1
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• pp.1-13
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• 2010

This paper describes a development of a fiber optic common-path optical coherence tomography (OCT) based imaging and guided system that possess ability to reliably identify optically transparent targets that are on the micron scale; ability to maintain a precise and safe position from the target; ability to provide spectroscopic imaging; ability to imaging biological target in 3-D. The system is based on a high resolution fiber optic Common-Path OCT (CP-OCT) that can be integrated into various mini-probes and tools. The system is capable of obtaining >70K A-scan per second with a resolution better than $3\;{\mu}m$. We have demonstrated that the system is capable of one-dimensional real-time depth tracking, tool motion limiting and motion compensation, oxygen-saturation level imaging, and high resolution 3-D images for various biomedical applications.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.130-136
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• 2015

We evaluate the influence of MR contrast agent on positron emission tomography (PET) image using phantom, animal and human studies. Phantom consisted of 15 solutions with the mixture of various concentrations of Gd-based MR contrast agent and fixed activity of [$^{18}F$]FDG. Animal study was performed using rabbit and two kinds of MR contrast agents. After injecting contrast agent, CT or MRI scanning was performed at 1, 2, 5, 10, and 20 minutes. PET image was obtained using clinical PET/CT scan, and attenuation correction was performed using the all CT images. The values of HU, PET activity and MRI intensity were obtained from ROIs in each phantom and organ regions. In clinical study, patients (n=20) with breast cancer underwent sequential acquisitions of early [$^{18}F$]FDG PET/CT, MRI and delayed PET/CT. In phantom study, as the concentration increased, the CT attenuation and PET activity also increased. However, there was no relationship between the PET activity and the concentration in the clinical dose range of contrast agent. In animal study, change of PET activity was not significant at all time point of CT scan both MR contrast agents. There was no significant change of HU between early and delayed CT, except for kidney. Early and delayed SUV in tumor and liver showed significant increase and decrease, respectively (P<0.05). Under the condition of most clinical study (< 0.2 mM), MR contrast agent did not influence on PET image quantitation.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.63-70
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• 2022

The development of myocardial perfusion imaging (MPI) agents has been motivated because coronary artery disease has been one of the leading causes of death worldwide since the 1960s. Several positron emission tomography (PET) MPI agents were developed, and ¹⁸F-labeled phosphonium cations were reported actively among them. In this study, we synthesized novel ¹⁸F-labeled phosphonium cations, (5-[¹⁸F]fluoropentyl)diphenyl(pyridin-2-yl)phosphonium and (2-(2-[¹⁸F]fluoroethoxy)ethyl)diphenyl(pyridin-2-yl)phosphonium, and evaluated potential as MPI agents. Two labeled compounds were synthesized via nucleophilic substitution reactions of ¹⁸F-fluoride with the appropriate tosylate precursor in the presence of Kryptofix 2.2.2 and K₂CO₃. MicroPET studies were performed in normal rats to evaluate in vivo distribution of radiolabeled phosphonium cations for 60 min. The radiolabeled compounds were synthesized with 5%-10% yield. The radiochemical purity of labeled compounds was > 98% by analytical HPLC, and the specific activity was > 11.8 GBq/µmol. The result of microPET studies of these labeled compounds in rats showed intense uptake in the myocardium at 30 and 60 min. The results suggest that these ¹⁸F-labeled novel phosphonium cations would have potential as promising candidates for myocardial perfusion imaging.

• IMMUNE NETWORK
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• v.12 no.6
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• pp.223-229
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• 2012

Clinical and preclinical in vivo immune cell imaging approaches have been used to study immune cell proliferation, apoptosis and interaction at the microscopic (intra-vital imaging) and macroscopic (whole-body imaging) level by use of ex vivo or in vivo labeling method. A series of imaging techniques ranging from non-radiation based techniques such as optical imaging, MRI, and ultrasound to radiation based CT/nuclear imaging can be used for in vivo immune cell tracking. These imaging modalities highlight the intrinsic behavior of different immune cell populations in physiological context. Fluorescent, radioactive or paramagnetic probes can be used in direct labeling protocols to monitor the specific cell population. Reporter genes can also be used for genetic, indirect labeling protocols to track the fate of a given cell subpopulation in vivo. In this review, we summarized several methods dealing with dendritic cell, macrophage, and T lymphocyte specifically labeled for different macroscopic whole-body imaging techniques both for the study of their physiological function and in the context of immunotherapy to exploit imaging-derived information and immune-based treatments.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.123-129
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• 2015

$^{64}Cu$-labeled diacetyl-bis($N^4$-methylthiosemicarbazone) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the study, we confirmed hypoxia regions in VX2 tumor implanted rabbits with injection $^{64}Cu$-ATSM and $^{18}F$-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with $^{18}F$-FDG and $^{64}Cu$-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of $^{64}Cu$-ATSM the acquired up to 48 hours. Correlation between intratumoral $O_2$ level and $^{64}Cu$-ATSM PET image was analyzed. $^{64}Cu$-ATSM and $^{18}F$-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, $^{64}Cu$-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for48 h. The uptake pattern of $^{64}Cu$-ATSM in VX2 tumor at 24 and 48 h did not match to the $^{18}F$-FDG. Through ROI analysis, in the early phase (dynamic scan), $^{18}F$-FDG has positive correlation with $^{64}Cu$-ATSM but late phase (24 and 48 h) of the $^{64}Cu$-ATSM showed negative correlation with $^{18}F$-FDG. High uptake of $^{64}Cu$-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by $^{64}Cu$-ATSM PET imaging and autoradiographic analysis. In conclusion, $^{64}Cu$-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue.