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Synthesis and evaluation of macrocyclic amino acid derivatives for tumor imaging by gallium-68 positron emission tomography.

Abstract：

:(68)Ga PET imaging in clinical oncology represents a notable development because the availability of (68)Ga is not dependent on a cyclotron. Furthermore, labeled amino acid derivatives have been proven to be useful for the imaging many tumor types. In the present study, we synthesized β-aminoalanine, γ-aminohomoalanine, and lysine conjugates of macrocyclic bifunctional chelating agents, such as, NOTA (1a-c) and DOTA (2a-c). The compounds produced were found to be potential useful as (68)Ga-PET imaging agents. In particular, they showed high tumor uptakes in vitro and in vivo, and had high labeling yields and excellent stabilities. The co-ordination chemistry of NOTA-monoamide compound 1a was studied by multinuclear NMR. In vitro studies showed that the synthesized compounds were taken up by cancer cells more than controls ((68)Ga-NOTA and (68)Ga-DOTA). Furthermore, in vivo studies showed that they have high tumor to muscle and tumor to blood ratios, and small-animal PET imaging revealed high tumor uptakes as compared with other organs, and high bladder activities, indicating rapid renal excretion. These results might motivate the use of (68)Ga amino acid PET for tumor diagnosis.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Shetty D,Jeong JM,Ju CH,Kim YJ,Lee JY,Lee YS,Lee DS,Chung JK,Lee MC

doi

10.1016/j.bmc.2010.09.022

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

7338-47

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(10)00849-7

journal_volume

18

pub_type

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