• 대한수의학회지
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• 제57권2호
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• pp.105-111
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• 2017

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350-400 nm) and larger HA polymers in mice at intervals after application. $^{177}Lutetium$ (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.

• 한국표면공학회:학술대회논문집
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• 한국표면공학회 2012년도 추계총회 및 학술대회 논문집
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• pp.86-87
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• 2012

폴리도파민이 다양한 표면을 개질할 수 있다는 것이 보고된 이래로, 폴리도파민을 이용한 다양한 응용 연구들이 계속되어 왔다. 본 연구에서는 이러한 폴리도파민을 이용하여 다양한 물질들로 오염된 물을 간단하고 효과적으로 정제하는 방법을 보고한다. 마이크로 크기의 실리카 비드에 폴리도파민을 코팅하여 흡착제로 사용하였으며, 이 흡착제가 다양한 중금속(Cu, Cr, Hg, Pb), 유기물질(4-Aminopyridine), 방사성 동위원소(Lutetium-177)를 효과적으로 흡착함을 확인하였다.

• 한국미생물·생명공학회지
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• 제41권4호
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• pp.469-471
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• 2013

본 연구를 통하여 우리는 새로운 실험기구를 사용하여 방사성동위원소(Lu-177)의 항균능력을 측정하였다. 기존에 약물의 항균능력을 측정하는데 사용되었던 디스크법은 배지로의 약물 확산에 의해서 항균능력을 측정하는 방법이기 때문에 방사성동위원소에 적용하기는 적합하지 않아 새로운 실험 방법이 요구된다. 방사성동위원소의 항균능력을 측정하기 위해서는 배지로의 약물 확산을 막고 한점에 머무르게 하는 방법이 필요하다. 본 연구에서 우리는 새로운 실험도구를 이용하여 Lu-177의 방사능량이 증가할수록 항균능력이 증가함을 확인하였다. 본 연구에서 사용된 실험방법을 통해 다른 방사성동위원소의 항균능력도 쉽게 측정할 수 있을 것으로 기대된다.

• 방사선산업학회지
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• 제9권4호
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• pp.187-192
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• 2015

CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the $^{177}Lu$-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with $^{177}Lu$ at room temperature within 15 minutes. The stability was tested in human serum. An in vitro study was carried out in HT-29 human colon cancer cell lines. For the biodistribution study $^{177}Lu$-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteine-based DTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50 kDa. Radioimmunoconjugation with $^{177}Lu$ was reacted for 15 min at room temperature. The radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with $^{177}Lu$. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

• 대한방사성의약품학회지
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• 제1권1호
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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.

• Korean Journal of Radiology
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• 제25권2호
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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.