摘要
我们研究DTPA-bis(蛋氨酸)的潜在作用,它是一种靶标特定的氨基酸探针,可使用多峰性成像技术检测在增殖肿瘤中过度表达的L-型氨基酸转运蛋白(LAT1)。它的配体,DTPA-bis(Met)容易转化为镧系配合物,且使用多峰性成像能够发现其靶向癌细胞。DTPA-bis(Met)配合物可被合成和被质谱表征。MR纵向弛豫, r1=4.067 ± 0.31 mM-1s-1 和横向弛豫,r2= 8.61 ± 0.07 mM-1s-1of Gd(III)-DTPA-bis(Met) 在 pH 7.4 和 7T下被检测。 Eu(III)-DTPA-bis(Met) 的光亮和局部荧光在标准显微镜下观察,位移研究表明配体功能。 Eu(III)-DTPA-bis(Met) 在U-87MG cells中的 KD值为17.3 pM,显示在细胞内有明显的荧光。放射HPLC显示68Ga(III)-DTPA-bis(Met) 的放射化学纯度超过 95% (具体活力 = 400-500 MBq/μmol, 标记效能 78 %)。用68Ga(III)-DTPA-bis(Met)和未标记的L-蛋氨酸对移植瘤的U-87MG无胸腺鼠的预处理使在Micro PET中的肿瘤摄入减少10倍。这些数据支持 68Ga(III)-DTPA-bis(Met)和 LAT1转运蛋白的特定绑定。总之,这种药物在生物环境中具有高度稳定性,并与在肿瘤区域高度积累的、高肿瘤/非肿瘤比率和体内非特定存留的LAT1转运蛋白间具有有效的相互作用。
关键词: 荧光,镧系,LAT1,蛋氨酸,PET成像。
图形摘要
Current Cancer Drug Targets
Title:LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities
Volume: 14 Issue: 9
Author(s): Puja Panwar Hazari, Surbhi Prakash, Virendra K. Meena, Ambika Jaswal, Harleen Khurana, Surabhi Kirti Mishra, Hemanth kumar Somu Bhonsle, Lokendra Singh and Anil K. Mishra
Affiliation:
关键词: 荧光,镧系,LAT1,蛋氨酸,PET成像。
摘要: We investigated the potential of DTPA-bis(Methionine), a target specific amino acid based probe for detection of L-type amino acid transporters (LAT1) known to over express in proliferating tumours using multimodality imaging. The ligand, DTPA-bis(Met) was readily converted to lanthanide complexes and was found capable of targeting cancer cells using multimodality imaging. DTPA-bis(Met) complexes were synthesized and characterized by mass spectroscopy. MR longitudinal relaxivity, r1=4.067 ± 0.31 mM-1s-1 and transverse relaxivity, r2= 8.61 ± 0.07 mM-1s-1of Gd(III)-DTPA-bis(Met) were observed at pH 7.4 at 7T. Bright, localized fluorescence of Eu(III)-DTPA-bis(Met) was observed with standard microscopy and displacement studies indicated ligand functionality. KD value determined for Eu(III)-DTPA-bis(Met) on U-87MG cells was found to be 17.3 pM and showed appreciable fluorescence within the cells. Radio HPLC showed a radiochemical purity more than 95% (specific activity = 400-500 MBq/μmol, labelling efficiency 78 %) for 68Ga(III)-DTPA-bis(Met). Pre-treatment of xenografted U-87MG athymic mice with 68Ga(III)-DTPA-bis(Met) following unlabelled L-methionine administration reduced tumour uptake by 10-folds in Micro PET. These data support the specific binding of 68Ga(III)-DTPA-bis(Met) to the LAT1 transporter. To summarize, this agent possesses high stability in biological environment and exhibits effective interaction with its LAT1 transporters giving high accumulation in tumour area, excellent tumour/non-tumour ratio and low non-specific retention in vivo.
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Puja Panwar Hazari , Surbhi Prakash , Virendra K. Meena , Ambika Jaswal , Harleen Khurana , Surabhi Kirti Mishra , Hemanth kumar Somu Bhonsle , Lokendra Singh and Anil K. Mishra , LAT1 Targeted Delivery of Methionine Based Imaging Probe Derived from M(III) Metal Ions for Early Diagnosis of Proliferating Tumours using Molecular Imaging Modalities, Current Cancer Drug Targets 2014; 14 (9) . https://dx.doi.org/10.2174/1568009614666141020102337
DOI https://dx.doi.org/10.2174/1568009614666141020102337 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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