Molar activity of radiopharmaceuticals

Choe, Yearn Seong 대한방사성의약품학회 2018 Journal of radiopharmaceuticals and molecular prob Vol.4 No.1

최근에 보고된 방사성의약품화학 분야의 명명법에 따라 그 동안 specific activity로 정의하였던 개념을 물리적인 성질을 나타내는 specific activity와 화학적 성질을 나타내는 molar activity로 세분하였다(1). 이 종설에서는 방사성의약품의 molar activity 및 중요성 등을 알아보았으며, 방사성의약품을 합성할 때 중요하게 고려하여야 한다. Radiopharmaceuticals are used for diagnosis or therapy of diseases. According to the recent consensus nomenclature rules for radiopharmaceutical chemistry, specific activity is defined as the radioactivity per gram of radiolabeled compound and molar activity as the radioactivity per mole of radiolabeled compound. In this review, molar activity of radiopharmaceuticals is discussed in terms of its significance in nuclear imaging as well as its measurement methods.

Development of an exclusive column method for 82Sr/82Rb generator using a 100 MeV proton linear accelerator of KOMAC

김계령,하영수,윤상필,이연지,조용섭,김현기,한상진,김정영,이교철,김진수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

82Sr for 82Rb generator was produced through the irradiation of the proton beam on the nat.RbCl target at the target irradiation facility installed at the end of the RI-dedicated beamline of the 100 MeV linear proton accelerator of KOMAC (Korea Multi-purpose Accelerator Complex). The size of the target was 7.5 mm thick and 30 mm in diameter, and the average current of the proton beam was 1.2 μA for irradiation time of 150 minutes. For the separation and purification of the 82Sr from nat.RbCl irradiated, Chelex-100 resin was used. The activities of 82Sr in the irradiated nat.RbCl target solution and after purification were 45.29 μCi and 43.4 μCi. The separation and purification yield was 95.8%. As an adsorbent to be filled in the generator STS316L column tube for 82Sr adsorption hydrous tin oxide was selected. The length of the column tube was 4 cm and the volume of the adsorbent was 1.76 cm3. The total length of the column including the inlet and outlet zero-volume adapters was 7.2 cm. The adsorption yield of 82Sr into the generator adsorbent was > 99 %, and the total amount of 82Sr adsorbed to the generator was 21.6 μCi as of the day of the 82Rb elution experiment. In the 82Rb elution experiment using saline, the 82Rb elution yield varies depending on the flow rate. When the elution amount was 22 mL, the 82Rb elution yield was 55.1 to 93.3%. When the flow rates were 5.0, 10.2, 14.5 and 22.0 mL/min, the yield was 55.1, 76.9, 86.2 and 93.3 %, respectively, and the elution yield increased as the flow rate increased. After the eluted 82Rb was filled in the correction phantom of the small PET for animals, a PET image was taken. The image scan time was set to 10 minutes, and the phantom PET image was successfully obtained. As results of impurity analysis on eluted 82Rb using ICP-MS, nat.Rb stable isotopes that compete in vivo of 82Rb were identified as undetected levels and were determined to be No-Carrier-Added (NCA).

Synthesis of a PEGylated tracer for radioiodination and evaluation of potential in tumor targeting

Abhinav Bhise,Sushil K. Dwivedi,이기웅,임정은,수브라므니 라즈쿠말,이웅희,조성환,유정수 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radio-tracer at the desired target excluding non-targeted tissues is difficult. The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG36) with the introduction of a low molecular weight polyethylene glycol unit (PEG36, ~2100 Da). The tumor-targeting efficiency and biodistribution of [131I]-Bz-PEG36 or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

Development of ⁶⁸Ga-human serum albumin as a PET imaging agent for diagnosis of acute inflammation

Lee, Ji Youn,Kim, Hoyoung,Lee, Boeun,Kim, Young Ju,Lee, Yun-Sang,Jeong, Jae Min 대한방사성의약품학회 2015 Journal of radiopharmaceuticals and molecular prob Vol.1 No.2

Human serum albumin (HSA) has potential for diagnosis and therapy in clinical setting. The purpose of experiments was to develop and evaluate $^{68}Ga$-HSA as a PET agent for diagnosis of acute inflammation. NOTA-HSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to HSA in 0.1 M sodium carbonate buffer (pH 9.5) and then purified using a PD-10 size-exclusion column. NOTA-HSA was labeled with $^{68}Ga$ at room temperature for 10 min, and 8.4% sodium hydrogen carbonate buffer was added for neutralization. $^{68}Ga$-NOTA-HSA was purified using alumina N plus light cartridge and $0.22{\mu}m$ syringe filter. Labeling efficiency and radiochemical purity were determined by ITLC-SG with 0.1 M citric acid. Biodistribution study was performed in a male BALB/c mice model of Carrageenan-induced acute inflammation. Animal PET study was performed in acute inflammation mice model after tail vein injection of $^{68}Ga$-HSA. This radiotracer showed high labeling efficiency (>99%) around pH 7. Biodistribution study showed higher inflamed footpad uptake than control footpad uptake. Animal PET study revealed 2 times higher uptake on inflamed footpad compared to control footpad. In these experiments, we developed $^{68}Ga$-HSA for acute inflammation PET imaging and evaluated it in a mouse disease model. The results demonstrated that $^{68}Ga$-HSA has potential as a PET imaging agent for diagnosis of acute inflammation.

Real-time identification of the separated lanthanides by ion-exchange chromatography for no-carrier-added Ho-166 production

김아란,최강혁 대한방사성의약품학회 2021 Journal of radiopharmaceuticals and molecular prob Vol.7 No.2

No-carrier-added holmium-166 (nca 166Ho) separation is performed based on the results of separation conditions using stable isotopes dysprosium (Dy) and holmium (Ho) to minimize radioactive waste from separation optimization procedures. Successful separation of two adjacent lanthanides was achieved by cation-exchange chromatography using a sulfonated resin in the H+ form (BP-800) and α-hydroxyisobutyric acid (α-HIBA) as eluent. For the identification process after separation of stable isotopes, the use of chromogenic reagents alternatively enables on-line detection because the lanthanides are hardly absorb light in the UV-vis region or exhibit radioactivity. Four different chromogenic reagents were pre-tested to evaluate suitable coloring reagents, of which 4-(2-Pyridylazo)resorcinol is the most recommendable considering the sensitivity and specificity for lanthanides. Lanthanide radioisotopes (RI) were monitored for separation with an RI detector using a lab-made separation LC system. Under the proper separation conditions, the nca 166Ho was effectively obtained from a large amount of 100 mg dysprosium target within 2 hrs.

Recent progress in aromatic radiofluorination

Kwon, Young-Do,Chun, Joong-Hyun 대한방사성의약품학회 2019 Journal of radiopharmaceuticals and molecular prob Vol.5 No.2

Fluorine-18 is considered to be the radionuclide of choice for positron emission tomography (PET). Thus, the development of small molecule-based radiopharmaceuticals for use in diagnostic imaging relies heavily on efficient radiofluorination techniques. Until the early 2000s, diaryliodonium salts and aryliodonium ylides were widely employed as labeling precursors to yield aromatic PET radiotracers with cyclotron-produced [¹⁸F]fluoride ion. Rapid recent progress in the development of efficient borylation methods has led to a paradigm shift in ¹⁸F-labeling methods. In addition, deoxyfluorination has attracted a great deal of interest as an alternative approach to aryl ring activation with ¹⁸F^-. In this review, methods for radiolabel development are discussed with a specific focus on the progress made in the last 5 years. Other interesting ¹⁸F-based protocols are also briefly introduced. New methods for exploiting ¹⁸F^- are expected to increase the number of ¹⁸F-labeling methods, to allow applications in a range of chemical environments.

Intratumoral distribution of 64Cu-ATSM and 18F-FDG in VX2 tumor xenografted rabbit

유란지,이지웅,이교철,안광일,오인옥,정위섭,박지애,김경민,최양규,강주현,임상무,이용진 대한방사성의약품학회 2015 Journal of radiopharmaceuticals and molecular prob Vol.1 No.2

64Cu-labeled diacetyl-bis(N4-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 64Cu-ATSM and 18F-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with 18F-FDG and 64Cu-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of 64Cu-ATSM the acquired up to 48 hours. Correlation between intratumoral O2 level and 64Cu-ATSM PET image was analyzed. 64Cu-ATSM and 18F-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, 64Cu-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for 48 h. The uptake pattern of 64Cu-ATSM in VX2 tumor at 24 and 48 h did not match to the 18F-FDG. Through ROI analysis, in the early phase (dynamic scan), 18F-FDG has positive correlation with 64Cu-ATSM but late phase (24 and 48 h) of the 64Cu-ATSM showed negative correlation with 18F-FDG. High uptake of 64Cu-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by 64Cu-ATSM PET imaging and autoradiographic analysis. In conclusion, 64Cu-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue. J Radiopharm Mol Probes 1(2):123-129, 2015

Radioiodination strategies for carborane compounds

Rajkumar Subramani,Abhinav Bhise,유정수 대한방사성의약품학회 2022 Journal of radiopharmaceuticals and molecular prob Vol.8 No.1

The development of methods for the inert and stable radiohalogenation of targeted radiopharmaceuticals is a prerequisite for real-time diagnosis and therapy using radiohalogenated radiopharmaceuticals. Radiohalogenated carboranes demonstrate superior stability in vivo and versatile applications compared with directly labeled tyrosine analogues or synthetically modified organic compounds. Herein, we focus on the most common approaches for the radioiodination (123I, 124I, 125I, and 131I) of carborane derivatives.

Kinetic analysis of ⁶⁴Cu-NODAGA-gluco-E[c(RGDfK)]₂ for a tumor angiogenesis PET tracer

Choi, Jae Yong,Park, Ji-Ae,Kim, Jung Young,Lee, Ji Woong,Lee, Minkyung,Shin, Un Chol,Kang, Joo Hyun,An, Gwang Il,Lee, Kyo Chul,Ryu, Young Hoon,Kim, Kyeong Min 대한방사성의약품학회 2016 Journal of radiopharmaceuticals and molecular prob Vol.2 No.2

Molecular imaging with the radiolabeled RGD peptides for ${\alpha}_v{\beta}_3$ integrin has been an increasing interest for tumor diagnosis and the treatment monitoring. Recently, $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ was developed for quantification of ${\alpha}_v{\beta}_3$ integrin and its biological properties was elucidated. To better understand the molecular process in vivo, we performed the kinetic analysis for the $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$. After preparation of a radiotracer, dynamic PET images were obtained in the U87MG xenograft mice for 60 min (n = 6). Binding potential values were estimated from the 3-tissue compartment model, reference Logan and simplified reference tissue model. In the early time frame (0-20 min), the liver, kidney, intestine, urinary bladder and tumor were visualized but these uptakes were diminished as time went by. The tumors showed a good contrast at 40 min after administration. $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ showed the 2-fold uptake in the tumor compared with that in the muscle. The parametric maps for binding values also provide the higher tumor-to-background contrast than the static images. A binding value obtained from the 3-tissue compartment model was comparable to other modeling methods. From these results, we conclude that $^{64}Cu$-NODAGA-gluco-E[c(RGDfK)]$_2$ may be a promising PET radiotracer for the evaluation of angiogenesis.

Validation of the production quality and therapeutic efficacy of 47Sc through its anti-cancer effects against EGFR-targeted non-small cell lung cancer

김다미,이소영,임재청,조은하,박울재 대한방사성의약품학회 2022 Journal of radiopharmaceuticals and molecular prob Vol.8 No.1

Anti-cancer and therapeutic effects using therapeutic radioisotopes have been demonstrated by various studies, and it is well-known that therapeutic radioisotopes are useful in cancer treatment. Recently, one of the therapeutic radioisotopes, scandium is emerging as a radioisotope applicable to PET imaging (43Sc, 44Sc) and therapy (47Sc) in cancer theranostic approach. However, 47Sc has little known radiobiological and therapeutic efficacy compared to other therapeutic radioisotopes. Here, we investigated the quality and therapeutic efficacy of 47Sc radioisotope produced by our production/isolation technology at the research reactor ‘HANARO’ in KAERI (Korea Atomic Energy Research Institute). We showed that the therapeutic efficacy of 47Sc, produced by our production/isolation technology, effectively suppressed epidermal growth factor receptor (EGFR)-targeted non-small cell lung cancer (NSCLC) cells. Consequently, these results suggest that the high quality of the produced 47Sc by our production/isolation technology enables the development of therapeutic strategies for cancer treatment and radiopharmaceuticals using 47Sc.