• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.84-95
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• 2016

Considerably increasing interest in using the theranostic isotopes/ isotope pairs of radiometals like $^{44/47}Sc$ and $^{64/67}Cu$ for diagnosis and/or therapeutic applications in the nuclear medicine procedures necessitates its reliable production and supply. Separation and purification of no-carrier-added (NCA) isotopes from macro quantitates of the irradiated target matrix along with other impurities is a cardinal procedure amongst several other steps involved in its production. Multitudinous methods including but not limited to liquid-liquid (solvent) extraction, extraction chromatography (EXC), ion exchange, electrodeposition and sublimation are routinely applied either solitarily or in combination for the separation and purification of radioisotopes depending on their production routes, radioisotope of interest and impurities involved. However, application of EXC though has shown promises towards the numerous separation techniques have not received much attention as far as its application prospects in the field of nuclear medicine are concerned. Advances in the recent past for application of the EXC resins in separation and purification of the several medically important radioisotopes at ultra-high purity have shown promising behavior with respect to their operation simplicity, acidic and radiolytic stability, separation efficiencies and speedy procedures with the enhanced and excellent extraction abilities. In this mini review we will be talking about the recent developments in the application and the use of EXC techniques for the separation and purification of $^{44/47}Sc$ and $^{64/67}Cu$ for medical applications. Furthermore, we will also discuss the scientific and practical aspects of EXC in the view of separation of the NCA trace amount of radionuclides.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.129-137
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• 2022

Bombesin has a high binding affinity to gastrin-releasing peptide receptor (GRPR) and can be used as a targeting ligand in GRPR-related cancers. Because GRPR is overexpressed in prostate cancer, bombesin analogues have been investigated extensively for diagnosis and treatment of prostate cancer. In nuclear medicine, bombesin derivatives labeled with radiometals such as ^55/57Co, ⁶⁴Cu, ⁶⁸Ga, ^99mTc, and ¹⁷⁷Lu or radiohalogen such as ¹³¹I and ²¹¹At were developed as markers for early detection of tumors and theragnostic tool for cancer treatment. This review focuses on the introduction of bombesin-based radiopharmaceuticals that are studied in pre-clinical or clinical research.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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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.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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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.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.145-151
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• 1996

Pathways both mediated by and independent of transferrin(Tf) and the TfR have been described for the accumulation of iron. Although it is not clear whether the same systems take up iron and gallium, these pathways may suggest the contention that uptake of Ga-67 can, in fact, occur by both Tf-independent and Tf-dependent systems and may share with Fe-59 in part the same mechanism for uptake. The predominant system by which uptake of both radiometals occurs may be different in the degree of the transformation of tumor. Transformed(MMSV/3T3) and untransformed(BALB/3T3) cells were incubated with luM of Ga-67-citrate of Fe-59-chloride for 15 min. at $37^{\circ}C$ in either the presence or absence of Tf. After then, the monolayers were washed with HBSS or PBS, and the cells were solubilized in 1% SDS for gamma well counting and protein determinations. There were similarities, as well as differences, in the pattern of uptake of Fe-59 and Ga-67 presented both in ionic from and as bound to Tf. Both radiometals appeared gain to cells in either ionic or Tf-bound forms. Transformed cells appeared to accumulate more radiometal, either Ga-67 or Fe-59 in the presence of Tf than do the their untransforemd counterparts. Conversly the presentation of either radiometal in ionic form resulted in significantly greater accumulation of metal by the untransformed cells than those transformed. The efficiency for uptake of Ga-67 or Fe-59 in the absence of Tf was greater than for uptake of the Ga-Tf or Fe-Tf. However, the magnitude of difference in efficiency of uptake was greater for Fe-59(10-fold) than for Ga-67 (3-fold). Our results Supports the theory that both Tf-independent and Tf-dependent systems for the uptake of Ga-67 both systems operate oppositely between transformed cells and those untransformed, with uptake by the predominating in transformed cells by the Tf-mediated system and in untransformed cells by the Tf-independent. The uptake of Ga-67 by tumor may share with Fe-59 in part the same mechanism.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.118-122
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• 2016

Integrin ${\alpha}_v{\beta}_3$ plays an important role in the tumor metastases and angiogenesis. Arginine-glycine-aspartate (RGD) peptide motif binds to the integrin ${\alpha}_v{\beta}_3$. General $^{68}Ga$-labeled cyclic RGD peptides was rapidly eliminated from the circulatory system by renal excretion because of its hydrophilic property. The purpose of this study was to develop a novel $^{68}Ga$-labeled cyclic RGD peptides, which could acquire enhanced PET tumor images with improved pharmacokinetics by adopting biphenyl group between chelator and RGD peptides. $^{68}Ga$-DOTA-2P-c(RGDyK) was demonstrated a 12% higher lipophilicity level than $^{68}Ga$-DOTA-c(RGDyK) as a reference compound. In the animal PET, $^{68}Ga$-DOTA-2P-c(RGDyK) represented relatively lower blood-clearance, and an increased signal to noise ratio compared to $^{68}Ga$-DOTA-c(RGDyK). From these perspective, $^{68}Ga$-DOTA-2P-c(RGDyK) could be a good candidate for in integrin ${\alpha}_v{\beta}_3$-expressed tumor imaging.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.44-48
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• 2005

Purpose: Ethylenediamine-tetramethylenephosphonic acid (EDTMP) has widely used chelator for the labeling of bone seeking radiopharmaceuticals complexed with radiometals. $^{153}Sm$ can be produced by the HANARO reactor at the Korea Atomic Energy Research Institute, Taejon, Korea. $^{153}Sm$ has favourable radiation characteristics $T1/2=46.7\;h,\;{\beta}_{max}=0.81\;MeV\;(20%),\;0.71\;MeV\;(49%),\;0.64\;MeV\;(30%)\;and\;{\gamma}=103\;keV\;(30%)$ emission which is suitable for imaging purposes during therapy. We investigated the labeling condition of $^{153}Sm$-EDTMP and imaging of $^{153}Sm$-EDTMP in normal rats. Materials and methods: EDTMP 20 mg was solved in 0.1 mL 2 M NaOH. $^{153}SmCl^3$ was added to EDTMP solution and pH of the reaction mixtures was adjusted to 3 and 12, respectively. Radiochemical purity was determined with paper chromatography. After 30 min. reaction, reaction mixtures were neutralized to pH 7.4, and the stability was estimated upto 120 hrs. Imaging studies of each reaction were perfomed in normal rats (37 MBq/0.1 mL). Results: The labeling yield of $^{153}Sm$-EDTMP was 99%. The stability of pH 8 reaction at 60, 96 and 120 hr was 99%, 95%, 89% and that of pH 12 at 36, 60, 96 and 120 hr was 99%, 95%, 88%, 66%, respectively. The $^{153}Sm$-EDTMP showed constantly higher bone uptake from 2 to 48 hr after injection. Conclusion: $^{153}Sm$-EDTMP, labeled at pH 8 reaction condition, has been stably maintained. Image of $^{153}Sm$-EDTMP at 2, 24, 48 hr after injection, demonstrate that $^{153}Sm$-EDTMP is a good bone seeking radiopharmaceuticals.