• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.53-58
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• 2020

Pretargeting is a two-component strategy often used for tumor targeting to enhance the tumor-to-background ratio in cancer diagnosis as well as therapy. In the multistep strategy, the highly specific unlabeled monoclonal antibodies (mAbs) with the reactive site is allowed to get localized at tumor site first, and then small and fastclearing radiolabeled chelator with counter reactive site is administered which covalently attaches to mAbs via inverse electron demand Diels-Alder reaction (IEDDA). The catalyst-free IEDDA cycloaddition reaction between 1,2,4,5-tetrazines and strained alkene dienophiles aid with properties like selective bioconjugation, swift and high yielding bioorthogonal reactions are emergent in the development of radiopharmaceutical. Due to its fast pharmacokinetics, the in vivo formed radioimmunoconjugates can be imaged at earlier time points by short-lived radionuclides like ¹⁸F and ⁶⁸Ga; it can also reduce radiation damage to the normal cells. Ultimately, this review elucidates the updated status of pretargeting based on antibodies and IEDDA for tumor diagnosis (PET and SPECT) and therapy.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.15-22
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• 2015

$^{18}F$-labeling reaction of bioactive molecule via click chemistry is widely used to produce $^{18}F$-labeled radiotracer in the field of radiopharmaceutical science and molecular imaging. In particular, bioorthogonal strain-promoted alkyne-azide cycloaddition (SPAAC) reaction has received much attention as an alternative ligation method for radiolabeling bioactive molecules such as peptides, DNA, proteins as well as nanoparticles. Moreover, SPAAC based pretargeting method could provide tumor images successfully on positron emission tomography system using nanoparticle such as mesoporous silica nanoparticles.

• Proceedings of the Korean Nuclear Society Conference
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• 2004.10a
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• pp.1257-1258
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• 2004

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.99.3-100
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• 2003

It is desirable to improve the tumor targeting and blood clearance pharmacokinetics of radiolabeled monoclonal antibodies. To achieve this goal, several avidin-biotin (Bt) binding systems have been developed to decouple large molecular weight antibodies from small radiolabels, thereby achieving high tumor-to-background radioactivity ratios. We inserted a readily catabolizable linker, triglycine (TG), between 3-［/sup125/I］iodobenzoate and dendrimer (G3). We also neutralized the positive charges of G3 by acylation with tetrafluorophenyl glycolate, thereby blocking proximal tubular reabsorption of G3 mediated by charge attraction. (omitted)

• The Korean Journal of Nuclear Medicine
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• v.26 no.2
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• pp.346-354
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• 1992

Cancer cells have several tumor-associated antigens on the cell surfaces, and antibodies against these antigens have been developed by many investigators. Radiolabeled antibodies have been used as new methods to diagnose and treat malignant tumors. Especially anti-carcinoembryonic antigen (CEA) is the most popular antibody for these purposes. In this investigation, we tried to label $^{131}I$ and $^{99m}Tc $ to anti-CEA monoclonal antibodies which were developed in the Seoul National University College of Medicine. We found CEA-79 and CEA-92 antibodies had the better immunological characteristics among 8 anti-CEA monoclonal antibodies. And radioiodination of CEA-79 could be performed by chloramine-T method, while radioiodination of CEA-92 by iodogen method. To label these antibodies with $^{99m}Tc $, we used pretargeting transchelation as direct labeling method. At first, $^{99m}Tc $ was bound to glucaric acid, and monoclonal antibody was reduced by $\beta-mercaptoethanol$. When these were incubated together. $^{99m}Tc $ bound to glucarate was switched to monoclonal antibody because of higher affinity. We established conditions of several steps in this method. Anti-CEA monoclonal antibodies labeled with $^{131}I$ and $^{99m}Tc $ are expected to be used valuably in the detection and treatment of malignant tumors.

• The Korean Journal of Nuclear Medicine
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• v.29 no.1
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• pp.98-104
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• 1995

Recently murine monoclonal antibodies have been studied actively for radioimmuno-scintigraphy and radioimmunotherapy, especially on patients with leukemia and lymphoma. In this research, we studied radiolabeling and immunologic characteristics of two in-house anti-leukemic monoclonal antibodies(anti-CALLA & anti-JL-1 antibodies) to make the basis for their clinical application. Each antibody was radiolabeled successfully with $^{99m}Tc$ by pretargeting transchelation method and with $^{125}I$ by lodogen method. We also studied cell binding assay, Scatchard analysis and modulation phenomenon. $^{125}I$ showed 90% labeling efficiency for each anti-body which was satisfactory, but $^{99m}Tc$ showed labeling efficiency below 70%, for which we need better labeling method. In cell binding assay, the immunoreactivity(IR) was low for $^{99m}Tc$-labeled antibodies. Scatchard analysis showed satisfactory data for both binding affinity. The affinity constant and antibody binding sites per cell are around $10^9M^{-1}$ and $10^4$, respectively. There was no modulation phenomenon in cases of $^{125}I$ or $^{99m}Tc$ labeled antibodies. We expect that two anti-leukemic monoclonal antibodies may be useful in diagnosis and therapy for leukemia and lymphoma patients.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.2
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• pp.74-81
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• 2006

Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its Interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect, the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. further development of this field will be determined by success in solving these challenges.