RT Journal Article
SR Electronic
T1 Different Modes of Transport for <sup>3</sup>H-Thymidine, <sup>3</sup>H-FLT, and <sup>3</sup>H-FMAU in Proliferating and Nonproliferating Human Tumor Cells
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1464
OP 1471
DO 10.2967/jnumed.110.076794
VO 51
IS 9
A1 Plotnik, David A.
A1 Emerick, Lindsay E.
A1 Krohn, Kenneth A.
A1 Unadkat, Jashvant D.
A1 Schwartz, Jeffrey L.
YR 2010
UL http://jnm.snmjournals.org/content/51/9/1464.abstract
AB The basis for the use of nucleoside tracers in PET is that activity of the cell-growth–dependent enzyme thymidine kinase 1 is the rate-limiting factor driving tracer retention in tumors. Recent publications suggest that nucleoside transporters might influence uptake and thereby affect the tracer signal in vivo. Understanding transport mechanisms for different nucleoside PET tracers is important for evaluating clinical results. This study examined the relative role of different nucleoside transport mechanisms in uptake and retention of [methyl-3H]-3′-deoxy-3′-fluorothymidine (3H-FLT), [methyl-3H]-thymidine (3H-thymidine), and 3H-1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl)-5-methyluracil (3H-FMAU). Methods: Transport of 3H-FLT, 3H-thymidine, and 3H-FMAU was examined in a single human adenocarcinoma cell line, A549, under both nongrowth and exponential-growth conditions. Results: 3H-Thymidine transport was dominated by human equilibrative nucleoside transporter 1 (hENT1) under both growth conditions. 3H-FLT was also transported by hENT1, but passive diffusion dominated its transport. 3H-FMAU transport was dominated by human equilibrative nucleoside transporter 2. Cell membrane levels of hENT1 increased in cells under exponential growth, and this increase was associated with a more rapid rate of uptake for both 3H-thymidine and 3H-FLT. 3H-FMAU transport was not affected by changes in growth conditions. All 3 tracers concentrated in the plateau phase, nonproliferating cells at levels many-fold greater than their concentration in buffer, in part because of low levels of nucleoside metabolism, which inhibited tracer efflux. Conclusion: Transport mechanisms are not the same for 3H-thymidine, 3H-FLT, and 3H-FMAU. Levels of hENT1, an important transporter of 3H-FLT and 3H-thymidine, increase as proliferating cells enter the cell cycle.