• Applied Chemistry for Engineering
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• v.28 no.2
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• pp.141-152
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• 2017

Inverse electron-demand Diels-Alder reactions (IEDDA) between tetrazine derivatives and strained dienophiles have attracted a lot of attention for the efficient conjugation of biomolecules, polymers, and nanomaterials. Excellent specificity, exceptionally fast reaction rate, and biocompatibility are key features of IEDDA. Therefore, it has also been applied to the development of new labeling methods using several radioisotopes and development of radiotracers to carry out various nuclear imaging as well as therapeutic studies. The purpose of this review is to introduce the reader to the recent advances and applications of IEDDA in the fields of radiochemistry and nuclear medicine.

• Journal of Radiation Industry
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• v.8 no.2
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• pp.77-81
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• 2014

Hyaluronic acid is a disaccharide polymer that consists of glucuronic acid and N-acetylglucosamine, and is a glycosaminoglycan. It is widely distributed in animal connective tissue, coexisting with chondroitin sulfate. It forms viscous secretions or gel by bonding to protein in the body, and thus maintains and lubricates tissue structures. In addition, its antibiotic properties are applied to cosmetics and pharmaceuticals. Therefore, it has recently been an object of great interest at cosmetic and pharmaceutical companies. $^{125}I$ has a longer half-life (59.4 days) than many other radioisotopes, and is therefore useful to long-term studies. In this study, a facile and efficient procedure for the synthesis of $^{125}I$-labeled hyaluronic acid has been designed for in vivo imaging and pharmacokinetic studies of hyaluronic acid, which are required for the development of new drugs.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.103-112
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• 2017

The combination of nanoparticle with radioisotope could give the in vivo information with high sensitivity and specificity. However, radioisotope labeling of nanoparticle is very difficult and radioisotopes have different physicochemical properties, so the radioisotope selection of nanoparticle should be carefully considered. $^{18}F$ was first option to be considered for labeling of nanoparticle. For the labeling of $^{18}F$ with nanoparticle, Prosthetic group is widely used. Iodine, another radioactive halogen, is often used. Since radioiodine isotopes are various, they can be used for different imaging technique or therapy in the same labeling procedures. $^{99m}Tc$ can easily be obtained as pertechnatate ($^{99m}{TcO_4}^-$) by commercial generator. Ionic $^{68}Ga$ (III) in dilute HCl solution is also obtained by generator system, but $^{68}Ga$ can be substituted for $^{67}Ga$ because of the short half-life (67.8 min). $^{64}Cu$ emits not only positron but also ${\beta}-particle$. Therefore $^{64}Cu$ can be used for imaging and therapy at the same time. These radioactive metals can be labeled with nanoparticle using the bifunctional chelator. $^{89}Zr$ has longer half-life (78.4 h) and is used for the longer imaging time. Unlike different metals, $^{89}Zr$ should use the other chelate such as DFO, 3,4,3-(LI-1,2-HOPO) or DFOB.

• Journal of Microbiology and Biotechnology
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• v.18 no.9
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• pp.1599-1605
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• 2008

Biodistribution and lymphoscintigraphy of cyclosporine A (CyA) and technetium-99m ($^{99m}Tc$) were studied using ${^99m}Tc$-labeled dextran acetate (DxA) including CyA. DxA particles were prepared from dextran with acetic anhydride, and CyA was loaded into them. Lymphatic delivery of ${^99m}Tc$-labeled DxA particles containing CyA was evaluated after subcutaneous injection into the foot pad of rats and compared with those of ${^99m}Tc$-labeled human serum albumin (HSA). The labeling efficiency of CyA-loaded ${^99m}Tc$-DxA particles was about 95% at 30 min. The labeling efficiency maintained stably above 80% for 12 h. The percent injected dose (%ID) of CyA-loaded ${^99m}Tc$-DxA was similar to that of ${^99m}Tc$-HSA at the inguinal lymph node after 40 min. The CyA-loaded ${^99m}Tc$-DxA could be as well distributed as ${^99m}Tc$-HSA through the lymph node. The DxA particles could steadily distribute the CyA as well as the ${^99m}Tc$ radiolabeling through the lymph node.

• Nuclear Engineering and Technology
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• v.38 no.5
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• pp.399-404
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• 2006

Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and $^{99m}Tc$ as a radionuclide. We developed $^{99m}Tc-galactosylated$ chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed $^{99m}Tc-HYNIC-chitosan-transferrin$ to target inflammatory cells, which was more effective than $^{67}Ga-citrate$ for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of $^{99m}Tc-HMPAO-labeled$ liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that $^{99m}Tc-labeled$ biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques.

• The Korean Journal of Nuclear Medicine
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• v.18 no.2
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• pp.77-85
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• 1984

Monoclonal antibodies have become widely investigated in the Nuclear Oncology, especially in the radioimmunosassay of tumor markers and in vivo radioimmunoimaging of cancer. However, there are numerous factors as to whether radioimmunoimaging will ultimately successful. For imaging of tumors, metallic radionuclides such as In-111, Ga-67, Tc-99m have favorable nuclear properties than widely used I-131. These radioistopes have characteristics of the useful radiation for imaging, convenient short half-lives and the simple and rapid radiolabeling of monoclonal antibodies by using bifunctional chelaing agents. The obtained chelate-tagged antibodies are quite stable both in vitro and in vivo, without interfering antibody activities and animal experiments provided a good basis for its clinical applicability for the radioimmunoimaging of cancer. Much attention has also been given to the possibility, only beginning to be exploited, of the specific treatment of malignant neoplasms with these agents. Although specific antibody has not been developed that is uniquely specific for cancer alone and there are still many questions to be answered and problems to be overcome before radioimmunoimaging can be successfully used in ptients with cancer, these methods can be applied to the coupling of monoclonal antibodies with anti-neoplastic drugs or radionuclides suitable for internal radiation therapy of cancer.

• Parasites, Hosts and Diseases
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• v.32 no.2
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• pp.101-110
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• 1994

This report describes the structures of high-mannose-type N-linked oligosaccharides in glycoproteins synthesized by the microfilariae of Diroflcrio immitis. Microfilariae of D. immitis were incubated in vitro in media containing 2-(3H) mannose to allow metabolic radiolabeling of the oligosaccharide moieties of newly synthesized glycoproteins. Glycopeptides were prepared from the radiolabeled glycoproteins by digestion with pronase and fractionation by chromatography on concanavalin A Sepharose. Thirty eight percent of 2- (3H) mannose incorporated into the microalariae of D. immitis glycopeptides was recovered in high mannose-type asparagine-linked oligosaccharides which were bound to the immobilized lectin. Upon treatment of 2-(3H) mannose labeled glycopeptides with endo - β- N- acetylglu co saminidase H , the high mannose type chains were released and their structures were determined by high performance liquid chromatography and exoglycosidase digestion. The major species of high mannose-type chains synthesized by microfilariae of D. immitis have the composition Man5GlcNAc2, Man6ClcNAc2, Man7GlcNAc2, and Man8GlcNAc2. Structural analyses indicate that these oligosaccharides are similar to high mannose-type chains synthesized by vertebrates.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6279-6284
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• 2015

Opisthorchis viverrini (OV)-induced cholangiocarcinoma (CCA) is an important cancer in the Great Mekong region, particularly in Thailand. Limitations of treatment options and the lack of an effective diagnostic tool for early detection of CCA are major concerns for the control of this type of cancer. The aim of the study was to investigate anti-CCA activity of the ethanolic extract of Atractylodes lancea (Thunb.) DC., and the applicability of positron emission tomography-computed tomography (PET-CT) as a tool for detection and monitoring the progression of CCA in Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN)-induced CCA hamsters. Male Syrian hamsters were used for toxicity tests and anti-CCA activity evaluation. Development of CCA was induced by initial feeding of 50 metacercariae of OV, followed by drinking water containing 12.5 ppm of DMN in hamsters. The ethanolic extract of A. lancea (Thunb.) DC. was administered orally for 30 days. PET-CT was performed every 4 weeks after initiation of CCA using 18F-fluorodeoxyglucose ($^{18}F-FDG$). Results from the present study suggest that the ethanolic extract of A. lancea (Thunb.) DC. rhizome exhibited promising anti-CCA activity and safety profile in the OV/DMN-induced hamster model. To successfully apply PET-CT as a tool for early detection of tumor development and progression, modification of radiolabeling approach is required to improve its specificity for CCA cells.

• Bulletin of the Korean Chemical Society
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• v.33 no.6
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• pp.1890-1894
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• 2012

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) have been implicated in the pathogenesis of rheumatoid arthritis, which is angiogenesis dependent. Antibody-based molecular imaging improves targeting, and antibody radiolabeling is useful for monitoring biological events $in$ $vivo$ $via$ PET or SPECT. We investigated the potential of molecular imaging to diagnose arthritis with VEGFR-2 $in$ $vivo$. The $^{123}I$-VEGFR-2 antibody was prepared by the iodogen tube method. The radioligand was injected into arthritic mice, and micro SPECT/CT was performed. The arthritic mice were examined by 4.7-T MRI and immunohistochemistry. The $^{123}I$-VEGFR-2 antibody showed high uptake in the arthritic region at 1 h postinjection on SPECT/CT but no uptake in the control animals after radioligand injection. In MR images, the arthritic tissue of the mice was correlated with regions labeled by the $^{123}I$-VEGFR-2 antibody. Immunohistochemical localization showed markedly increased expression of VEGFR-2 in the endothelial cells, fibroblasts, and macrophages of the arthritic mice.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.