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In vitro characterization of the thyroidal uptake of O-(2-[(18)F]fluoroethyl)-L-tyrosine.

Abstract：

OBJECTIVES:Positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) has been successfully employed in the diagnostic workup of brain tumors. Knowledge on the mechanisms of the uptake of radiolabeled amino acids into thyroidal tissues and well-differentiated thyroid carcinomas is limited. We therefore studied several factors potentially governing the uptake of FET in the rat thyroid cell line FRTL-5 in comparison with thyroid tumor cell lines of human origin. METHODS:FET uptake was determined in thyroid-stimulating hormone (TSH)-stimulated and TSH-deprived FRTL-5 cells, as well as in the cell lines U-138 MG (human glioblastoma), Onco DG-1 (human papillary thyroid carcinoma) and ML-1 (human follicular thyroid carcinoma). The TSH responsiveness of cells was measured by the incubation of TSH-treated and untreated control cells with 2-[(18)F]fluoro-2-deoxyglucose (FDG). All cellular tracer uptake values were related to total protein mass and expressed as percentage per milligram. For countertransport studies, FRTL-5 cells were exposed to 10-300 microM tyrosine methyl ester. TSH-stimulated and TSH-deprived FRTL-5 cells were incubated with 100 kBq/ml FET for 20 min. 2-Aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH), alpha-(methylamino)-isobutyric acid, L-serine and tryptophan were used as competitive inhibitors of FET uptake. All inhibition experiments were repeated with the human thyroid carcinoma cell lines to obtain comparative FET uptake values. RESULTS:The FET uptake was 155+/-30%/mg in FRTL-5 cells (n=6), 108+/-14%/mg in U-138 MG cells (n=6), 194+/-60%/mg in ML-1 cells (n=9) and 64+/-23%/mg in Onco DG-1 cells (n=6) under identical incubation conditions. Preloading with tyrosine methyl ester increased cellular FET uptake dose dependently in FRTL-5 cells (165+/-25%, n=6). While TSH increased the uptake of FDG in FRTL-5 cells by sixfold, there was no TSH effect on FET accumulation. FET uptake by TSH-treated FRTL-5 cells was sodium independent and significantly inhibited by BCH (91.4+/-3.0%, n=9), tryptophan (94.8+/-1.6%, n=8) and serine (83.2+/-10.8%, n=12). TSH-starved FRTL-5 cells had a sodium-dependent component with a similar inhibition pattern. Onco DG-1 mainly confirmed the inhibition pattern of FET uptake in FRTL-5 cells, reflecting System-L-mediated FET uptake that was blocked by BCH and serine (72-85%, n=9). ML-1 cells revealed a pronounced sodium-dependent FET uptake that was inhibited by tryptophan (70+/-10%, n=9, P<.05) in the presence and in the absence of sodium, suggesting a contribution of alternative amino acid carriers. CONCLUSION:FET uptake by FRTL-5 cells is not TSH dependent. FET uptake by FRTL-5 cells seems to be mainly mediated by a carrier exhibiting the characteristics of the System L amino acid transporter. FET uptake in thyroid cells and thyroid carcinoma cells was in the same range as that in a glioblastoma cell line. This encourages further research efforts towards the clinical evaluation of FET for the diagnostic workup of well-differentiated thyroid carcinomas.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Prante O,Bläser D,Maschauer S,Kuwert T

doi

10.1016/j.nucmedbio.2006.12.007

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

305-14

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(07)00006-6

journal_volume

pub_type

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In vitro characterization of the thyroidal uptake of O-(2-[(18)F]fluoroethyl)-L-tyrosine.