• 대한방사성의약품학회지
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• 제8권1호
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• pp.45-49
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• 2022

With the development of monoclonal antibodies, therapeutic or diagnostic radioisotope has been successfully delivered at tumor sites with high selectivity for antigens. Different approaches have been applied to improve the tumor-to-normal ratio by considering the in vivo stability of radioimmunoconjugates as a prerequisite. Various stable and inert antibody radiolabeling techniques for radioimmunoconjugate preparation have been extensively evaluated to enhance in vivo stability. Antibody radiolabeling techniques should be rapid and easy; they should not disrupt the immunoreactivity and in vivo behavior of antibodies, which are coupled with a bifunctional chelator (BFC) to stably coordinate with a radiometal. For the design of BFCs, radiometal coordination properties must be considered. However, various diagnostic radionuclides, such as ⁸⁹Zr, ⁶⁴Cu, ⁶⁸Ga, ¹¹¹ln, and ^99mTc, or therapeutic radionuclides, such as ¹⁷⁷Lu, ⁶⁷Cu, ⁹⁰Y, and ²²⁵Ac, have been increasingly used for antibody radiolabeling. In addition to useful radionuclides, ⁶⁴Cu and ¹⁷⁷Lu with the most accessible or the highest production rates in many countries should be considered. In this review, we mainly discussed antibody radiolabeling techniques and conditions that involve ⁶⁴Cu and ¹⁷⁷Lu radiometals.

• 대한핵의학회지
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• 제39권4호
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• pp.215-223
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• 2005

Current interest in the regioselective N-functionalization of tetraazacycloalkanes (cyclen and cyclam) stems mainly from their complexes with radioactive metals for applications in diagnostic ($^{64}Cu,\;^{111}In,\;^{67}Ga$) and therapeutic ($^{90}Y$) medicine, and with paramagnetic ions for magnetic resonance imaging ($Gd^{+3}$). Selective methods for the N-substitution of cyclen and cyclam is a crucial step in most syntheses of cyclen and cyclam-based radiometal complexes and bifunctional chelating agents. In addition, mixing different pendent groups to give hetero-substituted cyclen derivatives would be advantageous in many applications for fine-tuning the compound's physical properties. So far, numerous approaches for the regioselective N-substitution of tetraazacycloalkanes and more specifically cyclen and cyclam are reported. Unfortunately, none of them are general and every strategy has its own strong points and drawbacks. Herein, we categorize numerous regioselective N-alkylation methods into three strategies, such as 1) direct substitution of the macrocycle, 2) introductiou of the functional groups prior to cyclization, and 3) protection/iunclionallrationideproteclion. Our discussion is also split into the methods of mono- and tri-functionalization and di-functionalizataion based on number of substituents. At the end, we describe new trials for the new macrocycles which iorm more stable metal complexes with various radiometals, and briefly mention the commercially available tetraazacycloalkanes which are used for the biconjugation of biomolecules.

• 대한방사성의약품학회지
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• 제5권1호
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• pp.61-68
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• 2019

Purine type compounds has been recently reported to cause the death for lung cancer cell, related to microtubules-targeting agents (MTAs). Therefore it can be used to develop as theranostic radiopharmceuticals in nuclear medicine or gadolinium-based MRI imaging agents by chelate chemistry. In the study, we tried to chemically bind a DOTA chelate on the end of purine compound and obtained a specific conjugate of DOTA-purine for metal coordination. In particular, radiometal like Cu-64, for the development of MRI imaging agents, can be utilized to choice good candidates before the synthesis of gadolinium complexes. By the screening of radioisotope technique, Gd-DOTA-purine type complex was successfully prepared and showed MRI imaging for lung cancer cell into the mouse model.

• 대한방사성의약품학회지
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• 제5권2호
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• pp.79-82
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• 2019

⁶¹Cu is a promising PET radiometal having favorable nuclear decay characteristics with appropriate half-life of 3.3 h. Owing its promising capabilities in radiopharmaceutical chemistry and its chemical similarities with its isotopes ⁶⁴Cu and ⁶⁷Cu, in this work we have tried to optimize the production and separation conditions of ⁶¹Cu. ⁶¹Cu was produced via (p, x) reaction with natural nickel which was electroplated on the high purity silver coated copper backing target holder. The optimization of target electrodeposition, beam energy and current modulation, target dissolution and separation were optimized in this study. Preliminary studies show that ⁶¹Cu was successfully produced and separated which can be further extended for the production of ⁶⁴Cu and ⁶⁷Cu.

• 대한방사성의약품학회지
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• 제2권1호
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• pp.43-50
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• 2016

$^{89}Zr$ with the favorable nuclear decay kinetics and chemical properties is an appealing radiometal for its application in immuno-PET using radiolabeled monoclonal antibodies. Rising demand of ultrahigh purity and high-specific activity $^{89}Zr$ has propelled the radiochemist worldwide to develop an overall efficacious method for its promising separation from the target matrix $^{89}Y$. The requirement of elevated radiochemical purity (${\geq}$ 99.99%) has accelerated the efforts since last two decades to achieve higher decontamination and separation factors of carrier free $^{89}Zr$ over $^{89}Y$ using several suitable separation techniques. However, each of the technique has its own pros and cons which prior to its actual medical application needs to be optimized and thoroughly scrutinized to avoid further complications during radiolabelling of the pharmaceuticals. In this short review article we will specifically consider as well focus on the historical development and the recent advances on the radiochemical separation of $^{89}Zr$ from $^{89}Y$ which will be helpful for the separation scientist involved in this area to understand the existing available means and plan the strategy to investigate and develop the novel techniques to overcome the problems involved in the present methods.

• 대한방사성의약품학회지
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• 제3권2호
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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.

• 대한핵의학회지
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• 제30권1호
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• pp.145-151
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• 1996

철분이 축적하는데는 Tf나 Tf수용체에 의해 중재되는 경로와 비의존적인 경로가 둘 다 보고되어 왔다. 종양영상에 많이 사용되고 있는 Ga-67은 철분 유사 물질로 이러한 철분의 섭취 경로와 같은 경로에 의해 섭취되는지는 확실하지 않지만 Ga도 Tf의존성과 비의존성 섭취 경로가 보고되었으며 부분적으로는 철분과 같은 섭취경로를 공유할 수도 있다. 또한 종양의 변형정도에 따라 방사성 금속의 섭취기전이 다를 수도 있다. 변형세포로서 MMSV/3T3 세포와 비변형세포로서 BALB/3T3 세포를 Tf이 존재할때와 존재하지 않을 때에서 1uM의 Ga-67-citrate 혹은 Fe-59-chloride 와 함께 $37^{\circ}C$에서 15분간 배양하였다. 그 후 단일층의 세포를 HBSS로 3번, PBS로 1번 씻은 후 1% SDS로 용해시킨 후 감마카운터로 방사능을 측정한 후 단백질양을 측정하여 pmole metal/mg cellular protein으로 표시하였다. Fe-59와 Ga-67의 섭취양상은 71결합형과 이온형 둘다에서 크기의 차이는 있지만 비슷한 양상을 보였다. 즉 두 방사성 금속은 Tf 결합형과 이온형으로 세포로 들어간다. Tf과 함께 존재할 때는 철분이나 Ga 섭취가 변형세포에서 비변형세포에 비해 약 3배 이상 높았으나 Tf이 없이 이온형으로 존재할 때는 이와는 반대로 비변형세포에 의한 섭취가 변형세포에 비해 약4배 더 많았다. Ga-67이나 Fe-59의 섭취의 효율성은 Tf결합형인 Ga-Tf, Fe-Tf 형태가 이온형에 비해 약 10-15배 더 컸다. 그러나 섭취는 효율성의 크기는 Ga-67(3배)에 비해 Fe-59(10배)가 더 컸다. Ga-67의 섭취는 Tf의존성과 Tf비의존성 기전이 같이 존재하며 변형세포와 비변형세포는 서로 반대로 작용하였다. 즉 변형세포의 섭취는 Tf의존성 기전에 의하고, 비변형세포의 섭취는 Tf 비의존성 기전에 의해 주로 일어나며 종양조직에 의한 Ga-67의 섭취 기전은 부분적으로는 Fe-59와 같은 섭취기전을 공유할 수 있다고 생각되었다.