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

Abstract：

PURPOSE:We evaluated new (111)In-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 (111)In. 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 (111)In-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 (111)In-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. (111)In-DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean tumor-to-muscle ratio 3.16±0.74). Autoradiography and immunohistochemistry revealed that (111)In-DO3A-H uptake matched L-type amino acid transporter 1 expression. CONCLUSION:Tumor uptake was successfully imaged using (111)In-DO3A-H in U87MG bearing xenografted mice. (111)In-DO3A-H appears to be useful for imaging tumors expressing L-type amino acid transporter.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Lee JJ,Shetty D,Lee YS,Kim SE,Kim YJ,Hong MK,Son JY,Jeong JM

doi

10.1016/j.nucmedbio.2011.09.010

subject

Has Abstract

pub_date

2012-04-01 00:00:00

pages

325-33

issue

3

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(11)00231-9

journal_volume

39

pub_type

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