• 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.6 no.1
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• pp.46-52
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• 2020

Radiopharmaceuticals that can be consumed in specific disease site play a key role In order to diagnose and treat the diseases. In addition, radiopharmaceuticals can be used for diagnostic or therapeutic purposes depending on the type of the labeled radioactive isotope. Recently, theragnostic radiopharmaceuticals that can simultaneously diagnose and treat are developed. Therefore, the development of target-specific radiopharmaceuticals is a very important research topic in the field of molecular imaging and therapy. This review paper summarizes the basic considerations for the development of radiopharmaceuticals. For new researchers or students who are now beginning in the field of radiopharmaceuticals, we intend to assist in the development of radiopharmaceuticals by describing the definition of radiopharmaceuticals, the ideal radiopharmaceutical conditions, the considerations for developing new radiopharmaceuticals, the factors affecting the design of radiopharmaceuticals, the requirements of radioisotope labeling reactions, and finally the definition and importance of molar activity in radiopharmaceuticals.

• Korean Journal of Radiology
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• v.25 no.2
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• Journal of radiological science and technology
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• v.43 no.1
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• pp.35-43
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• 2020

The purpose of this study was to study on radiologic technologist's license system and primary pathway education curriculum in the United States American (USA), focused on one case of college in Texas. We were collected and analyzed through class participation at a community college in Tarrant, interviews with professors of radiologic science and clinical radiographers, field trips, an internet search, and literature reviews. As a result, first, the American radiologic technologists license system is composed of fifteen chapters, and the professional education courses for each field are being carried out through three courses of a primary pathway, a post primary pathway and a physician extender. Second, the primary pathway courses consisted the radiography, the radiation therapy, the nuclear medicine, the magnetic resonance imaging, the sonography. Third, the USA had about 30 times more clinical practice time than Korea. In clinical practice, students had done actually examination through X-ray exposure on patients. Last radiographers in the USA was able to perform intravenous injection of radiopharmaceutical agents on patient, so that he could perform rapid examination and efficient manpower operation. This study could be used as basic data for the globalization of radiologic technologists license system in Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7441-7447
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• 2015

Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

• Korean Journal of Digital Imaging in Medicine
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• v.12 no.2
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• pp.113-117
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• 2010

This research attempts to qualitatively evaluate the intensity change by radiopharmaceuticals and obtain computed tomography using phantom injected with various nuclide. Cylindrical phantom is used for comparing and analysing the effect on diagnosis image during radiopharmaceuticals inspection. Inside of the phantom, water is injected and computed tomography image is scanned. During nuclear medicine invitro, frequently used radiopharmaceuticals, $^{99m}TcO_4$ 20 mCi and $^{18}F$ 14 mCi, is diluted in the water phantom and scanned in the same method. Traverse image obtained by CT scan is divided into six traverse image in the same slice of each scanned image. CT-number(HU) value of 10 measuring point is measured in 2 cm interval based on the center of the phantom. Measured HU value, based on the water phantom, is compared with the image after injecting $^{99m}TcO_4$ and $^{18}F$. Average scale of water is 2.8~1.6 HU, $^{99m}TcO_4$ is 3.0~1.6 HU and $^{18}F$ is 1.2~0 HU. Average of water is $2.3{\pm}0.17$ HU, $^{99m}TcO_4$ is $2.2{\pm}0.85$ HU and F-18 is $0.7{\pm}0.95$ HU. Based on water, reduced value of about 0.1 HU and about 0.5 HU is acquired from $^{99m}TcO_4$ and F-18. Radionuclide used in nuclear medicine inspection utilizes 100~200 KeV energy and obtains image through scintillation camera and PET-CT utilizes 511 KeV positron annihilation energy to obtain image. What we learned from this research is that gamma rays from these energies used in CT scan for diagnosis purpose or radioactive therapy plan can change the intensity of the image. The nuclear medicine inspection for reducing the effect of emitted gamma ray diagnosis image should be obtained after a period of time considering half-life which would be reduced distortion or changed in image.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.17-21
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• 2023

In this study, we evaluated the targeting of prostate cancer (PCa) using [¹⁸F]Florastamin in non-clinical study, for the purpose of therapeutic monitoring of [¹⁷⁷Lu]Ludotadipep, a therapeutic radiopharmaceutical for PCa, [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was co-administered to a single-individual prostate tumor bearing mouse model, mimicking clinical condition. Considering the difference in half-life of the two isotopes (¹⁸F or ¹⁷⁷Lu), image scan of whole-body autoradiography was performed at 24 or 48 h after preparation of frozen section, respectively. Then, it was confirmed whether they showed the same targeting efficiency for the area of tumor. A tumor xenograft model was prepared using PSMA-overexpressing PC3-PIP prostate cancer cells. [¹⁸F]Florastamin [111 MBq (3 mCi) in 100 µL]/¹⁷⁷Lu]Ludotadipep [3.7 MBq (100 µCi) in 100 µL] was co-administered through the tail vein, and 2 hours after administration, the mice were frozen, and after freezing for 24 hours, whole-body cryosection was performed at 24 h after freezing. Image scanning using cryosection was performed after 24 or 48 hours after freezing, respectively. In the scan image after 24 hours, tumor uptake of [¹⁸F] Florastamin/[¹⁷⁷Lu]Ludotadipep were simultaneously observed specific uptake in the tumor. In the scan image after 48 hours in the same section, signal of ¹⁸F was lost by decay of radioisotope, and specific uptake image for [¹⁷⁷Lu]Ludotadipep was observed in the tumor. Uptake of [¹⁷⁷Lu]Ludotadipep was specific to the same tumor region where [¹⁸F]Florastamin/[¹⁷⁷Lu]Ludotadipep was uptake. These results suggested that [¹⁸F]Florastamin showed the same tumor uptake efficiency to PCa as [¹⁷⁷Lu]Ludotadipep, and effective therapeutic monitoring is expected to be enable using [¹⁸F]Florastamin during [¹⁷⁷Lu]Ludotadipep therapy for PCa.

• The Korean Journal of Nuclear Medicine
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• v.37 no.5
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• pp.301-307
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• 2003

Purpose: Lipiodol is used for targeting liver cancers by administrating through the hepatic artery. In the present study, feasibility of Re-188-sulfur colloid suspension in lipiodol as a liver cancer targeting agent was investigated. Materials and Methods: Re-188-sulfur colloid was prepared, harvested by centrifugation, washed with organic solvent and then suspended into lipiodol. Biodistribution of Re-188-sulfur colloid in normal saline and its suspension in lipiodol in mice after 1 hr of injection through the tail vein were investigated. Biodistribution and autoradiography of tumor-hearing liver was acquired after 5 min post-injection into left ventricle of the tumor-inoculated rats. Results: After 1 hr of injection with Re-188-sulfur colloid suspensiob in lipiodol through the tail vein in normal mice (n=3), the uptakes in the liver and lung were $5.2{\pm}0.7\;and\;91.0{\pm}1.7%$ ID/organ, respectively. After 5 min of injection with Re-188-sulfur colloid suspention in lipiodol through the left ventricle in the tumor-inoculated rats (n=4), uptakes in the normal liver, hepatoma, and lung were $0.41{\pm}0.28,\;1.88{\pm}1.57,\;and\;1.65{\pm}1.54%$ ID/organ, respectively. And autoradiography of hepatoma showed increased uptake than normal liver tissues. Conclusion: Re-188-sulfur colloid suspension in lipiodol injected through the artery shows higher uptake in the hepatoma than normal liver tissue that indicates the feasibility as a new radiopharmaceutical for therapy of hepatoma.

• Journal of the Korean Society of Radiology
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• v.9 no.5
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• pp.323-329
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• 2015

This study is aimed at assessing whether dynamic wedge filters are appropriate to be used instead of physical wedge filters. The X-ray energy generated from linear accelerator is commercialize 6 MV and 10 MV. $15^{\circ}$, $30^{\circ}$, $45^{\circ}$, and $60^{\circ}$ of physical wedge filter was irradiated by dose rate 100, 200, 300, 400, 500, and 600 MU/min for each angle and for comparison with a dynamic wedge filter, irradiate 96 times under the same conditions. The measurement conditions are as 100 cm source-film distance and $10{\times}10cm$ irradiated surface. A developed film was scanned and analyzed after a calibration through a dose analysis program and the dose rate was compared after calculating the standard deviation. Dynamic wedge filters make dose, scattered rays and treatment time reduced and very useful due to less irradiated doses to patients. The errors at each dose rate under the same conditions were irrelevant. Thus, treatment based on a high dose rate depending on the patient is expected to be feasible.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.53-61
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• 2015

Lutetium-177 ($T_{1/2}=6.71day$) is an adequate radionuclide for therapy, which has both beta emission ($E_{max}=497keV$) for therapeutic effect and gamma emission (113 and 208 keV) for imaging. $^{177}Lu$ labeled ethylenediamine-N,N,N',N'-tetrakis (methylene phosphonic acid) (EDTMP) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminomethylenephosphonate (DOTMP) have been proposed as radiopharmaceuticals for bone pain palliation. In this study, we compared radiochemistry and biodistribution of $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP. EDTMP and DOTMP were synthesized, and 1 mg of each was labeled with $^{177}Lu$ at pH 7~8 with high efficiency (>98%). For comparative biodistribution studies, $^{177}Lu$-EDTMP or $^{177}Lu$-DOTMP were injected into ICR-mice through tail vein, and then biodistribution data were obtained as percentages of injected dose per gram of tissue (% ID/g). Urine excretions of both agents in mice were checked for 7 days. Rat images were also obtained after injection of $^{177}Lu$-EDTMP or $^{177}Lu$-DOTMP. $^{177}Lu$-DOTMP (100% at 1 min) showed faster labeling than $^{177}Lu$-EDTMP (100% at 30 min). Both of them were stable at least for 21 days at room temperature. High bone uptakes were found for both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP: 38.0 and 34.1% ID/g at 3 hr, respectively; and 33.2 and 18.8% ID/g at 7 day, respectively. Rapid excretions to urine were found for both agents ($^{177}Lu$-EDTMP: 56%, $^{177}Lu$-DOTMP: 63% at 1 day). Other organs showed very low uptakes. Rat images of both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP showed high bone uptakes and low soft tissue uptakes. In conclusion, both $^{177}Lu$-EDTMP and $^{177}Lu$-DOTMP showed high potential as bone pain palliation agents. $^{177}Lu$-EDTMP showed higher bone uptake and slower bone clearance in mice than those of $^{177}Lu$-DOTMP.