当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid.

System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid.

Abstract：

INTRODUCTION:Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural (18)F-labeled amino acids, (R)- and (S)-[(18)F]FAMP 1 and (R)- and (S)-[(18)F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET). METHODS:The transport of enantiomers of [(18)F]FAMP 1 and [(18)F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection. RESULTS:All four tracers showed moderate to high levels of uptake (1-9%ID/5×10(5) cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[(18)F]1 and (S)-[(18)F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[(18)F]2 and (S)-[(18)F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors. CONCLUSIONS:These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[(18)F]2 having the highest selectivity for system A AAT.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Yu W,McConathy J,Olson JJ,Goodman MM

doi

10.1016/j.nucmedbio.2014.07.002

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

8-18

issue

1

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(14)00453-3

journal_volume

42

pub_type

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