177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research)(177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research))

概要

基本信息

药物类型

核素偶联药物、治疗用放射药物

别名

177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250

靶点

CASP family

作用机制

caspase抑制剂(半胱天冬酶家族抑制剂)、电离辐射发射源

治疗领域

肿瘤泌尿生殖系统疾病

在研适应症-

非在研适应症

转移性肾细胞癌

原研机构

Ludwig Institute for Cancer Research Ltd.

在研机构-

非在研机构

Ludwig Institute for Cancer Research Ltd.

最高研发阶段无进展临床1/2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

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关联

1

项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的临床试验

NCT00142415

/ Completed临床1/2期IIT

Phase I/II Study of Increasing Doses of Lutetium-177 Labeled Chimeric Monoclonal Antibody cG250 (177^Lu-DOTA-cG250) in Patients With Advanced Renal Cancer

This was a Phase I/II, single-center, dose-escalation study. 177-Lutetium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-cG250 (177-Lu-DOTA-cG250) was administered at a starting dose of 30 mCi/m^2 of 177-Lu (fixed dose of 10 mg cG250) and escalated in increments of 10 mCi/m^2 of 177-Lu in sequentially enrolled cohorts according to a standard 3 + 3 design until determination of the maximum tolerated dose (MTD). The primary objectives were to determine the safety, targeting, and dosimetry of 177-Lu-DOTA-cG250 in subjects with advanced renal cell carcinoma. The secondary objective was measurement of tumor response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

开始日期2005-02-01

申办/合作机构

Ludwig Institute for Cancer Research Ltd.

[+1]

100 项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的临床结果

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100 项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的转化医学

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100 项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的专利（医药）

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301

项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的文献（医药）

2025-01-01·Bioorganic Chemistry

Synthesis and bioevaluation of a new 68Ga-labelled niraparib derivative that targets PARP-1 for tumour imaging

Article

作者: Wang, Qianna ; Han, Peiwen ; Jiang, Yuhao ; Li, Zuojie ; Yin, Guangxing ; Feng, Junhong ; Ruan, Qing ; Zhang, Junbo

Poly ADP-ribose polymerase (PARP) inhibitors prevent the repair of DNA single-strand breaks in cancer cells with abnormal homologous recombination, producing a synthetic lethal effect. Thus, PARP inhibitors have become clinically effective anticancer drugs. Labelling with radionuclides may extend the use of PARP inhibitors as tracers in nuclear medicine diagnostics, helping to stratify patients. In the present study, niraparib was selected as a skeleton molecule modified with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labelled with gallium-68 to obtain [⁶⁸Ga]Ga-DOTANPB with high radiochemical purity (>95 %). To verify the accuracy of the [⁶⁸Ga]Ga-DOTANPB structure, [^natGa]Ga-DOTANPB was also synthesized, and in vitro affinity experiments were performed, which revealed a high affinity for PARP-1 (IC₅₀ = 82.21 nM). [⁶⁸Ga]Ga-DOTANPB is hydrophilic and has good in vitro stability within 3 h. In in vitro experiments, [⁶⁸Ga]Ga-DOTANPB has a high uptake in HeLa cells and can enter the cell to target PARP-1. In coronal PET imaging of HeLa tumour-bearing mice, [⁶⁸Ga]Ga-DOTANPB showed significant radioconcentration at the tumour site at 0.5 h, 1 h, and 2 h. Biodistribution and autoradiography experiments revealed that [⁶⁸Ga]Ga-DOTANPB has obvious tumour uptake and can be significantly inhibited (3.37 ± 0.33 % ID/g vs. 2.50 ± 0.27 % ID/g, **P < 0.01), suggesting that it has PARP-1 specificity. Thus, these findings suggested that [⁶⁸Ga]Ga-DOTANPB may be a potential niraparib-based PET tracer for targeting PARP-1.

2024-11-20·Bioconjugate Chemistry

Click Chemistry Enables [⁸⁹Zr]Zr-DOTA Radioimmunoconjugation for Theranostic ⁸⁹Zr-immunoPET

Article

作者: Jang, Jaewoong ; Akimitsu, Nobuyoshi ; Takahashi, Hiroyuki ; Wada, Youichiro ; Kumakura, Yoshitaka ; Imura, Ryota ; Ozeki, Atsuko Nakanishi ; Ida, Hiroyuki

There have been predictions that the use of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in zirconium-89 (⁸⁹Zr) immuno-positron emission tomography (⁸⁹Zr-immunoPET) could enhance the in vivo stability of ⁸⁹Zr radioimmunoconjugates. However, conjugating [⁸⁹Zr]Zr-DOTA to a monoclonal antibody (mAb) remains a challenge as the heat treatment required for [⁸⁹Zr]Zr-DOTA chelation can lead to thermal denaturation of the mAb moieties. We developed a method for synthesizing [⁸⁹Zr]Zr-DOTA-mAb based on a tetrazine (Tz)-conjugated bifunctional DOTA derivative 2,2',2″-(10-(1-(4-(1,2,4,5-tetrazin-3-yl)phenyl)-3,21,26-trioxo-6,9,12,15,18-pentaoxa-29-carboxy-2,22,25-triazanonacosane-29-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-Tz) and the inverse electron-demand Diels-Alder (IEDDA) click chemistry reaction where trans-cyclooctene-modified mAbs are conjugated to [⁸⁹Zr]Zr-DOTAGA without being exposed to heat. The stability of IEDDA-derived [⁸⁹Zr]Zr-DOTAGA-trastuzumab was confirmed by in vitro, ex vivo, and in vivo testing and comparative analysis against the conventional deferoxamine (DFO) counterpart [⁸⁹Zr]Zr-DFO-trastuzumab. The in vivo immunoPET imaging using [⁸⁹Zr]Zr-DOTAGA-trastuzumab clearly visualized human epidermal growth factor receptor 2-positive malignancies in murine xenograft models. Greater tumor contrast was observed from [⁸⁹Zr]Zr-DOTAGA-trastuzumab at a 72-h delayed scan compared with [⁸⁹Zr]Zr-DFO-trastuzumab. These findings suggest that our IEDDA ligation approach can be an effective means of synthesizing [⁸⁹Zr]Zr-DOTA-mAb and can enhance the theranostic potential of ⁸⁹Zr-immunoPET in DOTA-mediated radioimmunotherapy.

2024-10-01·Nuclear Medicine Communications

Internal dosimetry and biodistribution of indigenously prepared 177Lu-DOTA-rituximab in lymphoma and other hematological malignancies treated with rituximab

Article

作者: Sahu, Sudeep ; Edamadaka, Yeshwanth ; Basu, Sandip ; Parghane, Rahul V. ; Lad, Sangita ; Shanmukhaiah, Chandrakala ; Kamaldeep ; Wanage, Gaurav ; Kulkarni, Vrinda

ObjectiveThe aim of this study was to evaluate the biodistribution and dosimetry of lutetium-177-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (177Lu-DOTA)-rituximab in CD20+ non-Hodgkin’s lymphoma and other hematological malignancies treated with rituximab.MethodsThe standard dosimetry protocol was used, with cold rituximab infusion, then a diagnostic activity of 177Lu-DOTA-rituximab. Planar images were acquired at multiple time points. Normal organs and tumor dosimetry were performed by using organ and tumor-specific regions of interest and whole-body counts were obtained serially after pixel matched, background, scatter, and attenuation correction. The mean radiation absorbed doses were obtained from OLINDA/EXM v2.1.1 and ORIGIN software.ResultsA total of 22 patients were included in this study. Prolonged blood pool clearance of 177Lu-DOTA-rituximab with long residence time in the blood pool and normal organs were observed. The whole body effective half-life was 104.5 ± 22 h. The mean total body radiation absorbed dose was 0.208 ± 0.03 mGy/MBq and the mean total body effective dose was 0.196 ± 0.05 mGy/MBq of 177Lu-DOTA-rituximab. The mean radiation absorbed doses of 0.613 ± 0.21, 1.68 ± 2, 1.01 ± 0.42, and 0.136 ± 0.02mGy/MBq were seen for the liver, spleen, kidneys, and bone marrow, respectively. Tumor lesion uptake was noticed in two patients with tumor radiation absorbed doses were 0.842 mGy/MBq in one and 9.9 mGy/MBq in the other patient. A strong correlation was obtained between the cumulative activities of radiation-absorbed doses derived from ORIGIN and OLINDA software methods at a significant P value less than 0.001.ConclusionThe results of our study demonstrated favorable biodistribution and dosimetry of indigenously produced 177Lu-DOTA-rituximab in patients with CD20+ lymphoma. These results can be used for future studies of radioimmunotherapy employing 177Lu-DOTA-rituximab.

100 项与 177-Lu-DOTA-cG250(Ludwig Institute for Cancer Research) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性肾细胞癌	临床2期	荷兰	Ludwig Institute for Cancer Research Ltd.	2005-02-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00142415 (CTgov)	临床1/2期	转移性肾细胞癌	26	111-In-DOTA-cG250+177-Lu-DOTA-cG250 (Cohort 1, 30 mCi/m^2 177-Lu-DOTA-cG250)	糧鹹選襯窪夢築窪願糧(醖鏇壓觸積積鑰糧觸淵) = 鏇鏇鹽窪淵糧鬱鏇顧積願膚蓋廠淵襯淵廠憲簾 (鑰築積鹹艱醖積範構網, 願淵築醖窪壓憲壓鹹獵 ~ 觸襯範鬱膚廠製構鬱齋) 更多	-	2017-03-22
				111-In-DOTA-cG250+177-Lu-DOTA-cG250 (Cohort 2, 40 mCi/m^2 177-Lu-DOTA-cG250)	糧鹹選襯窪夢築窪願糧(醖鏇壓觸積積鑰糧觸淵) = 糧蓋鏇餘壓醖醖範製鏇願膚蓋廠淵襯淵廠憲簾 (鑰築積鹹艱醖積範構網, 願襯範襯廠觸繭憲構膚 ~ 遞餘鑰積窪繭衊壓窪夢) 更多