Evaluation of ¹¹¹In-labeled macrocyclic chelator-amino acid derivatives for cancer imaging

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• 作者：Jong Jin Lee^a ; ^b ; ^c ; Dinesh Shetty^a ; Yun-Sang Lee^a ; Sang Eun Kim^c ; Young Joo Kim^a ; Mi Kyung Hong^a ; Ji Yeon Son^c ; Jae Min Jeong^a ; ^{jmjng@snu.ac.kr}
• 关键词：Indium-111 ; DO3A ; Homoalanine ; SPECT ; Amino acid ; LAT ; DOTA ; Amino acid transporter
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：April, 2012
• 卷：39
• 期：3
• 页码：325-333
• 文件大小：953 K

摘要

Purpose

We evaluated new ¹¹¹In-labeled amino acid derivatives, in which the amino acids are conjugated with1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) or 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A).

Methods

DOTA-aminoalanine (DOTA-A), DOTA-aminohomoalanine (DOTA-H), DOTA-lysine (DOTA-L), DO2A-alanine (DO2A-A), DO3A-alanine (DO3A-A) and DO3A-homoalanine (DO3A-H) were labeled with ¹¹¹In. In vitro cell uptake assays were performed usingHep3B (a human hepatoma cell line), CT26 (a mouse colon cancer cell line) and U87MG (a human glioma cell line). In vitro cell uptake inhibition assays were performed using U87MG and ¹¹¹In-DO3A-H. U87MG bearing xenografted mice were subject to biodistribution, SPECT imaging, autoradiography, and immunohistochemistry studies.

Results

Of the amino acid derivatives and cell lines examined, U87MG and ¹¹¹In-DO3A-H showed highest uptake in vitro. This uptake was blocked by 2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid (BCH) and by tryptophan. ¹¹¹In-DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean tumor-to-muscle ratio 3.16卤0.74). Autoradiography and immunohistochemistry revealed that ¹¹¹In-DO3A-H uptake matched L-type amino acid transporter 1 expression.

Conclusion

Tumor uptake was successfully imaged using ¹¹¹In-DO3A-H in U87MG bearing xenografted mice. ¹¹¹In-DO3A-H appears to be useful for imaging tumors expressing L-type amino acid transporter.