Cell uptake and tissue distribution of radioiodine labelled D-luciferin: implications for luciferase based gene imaging.
Optical luciferase gene imaging is emerging as a method to monitor gene expression in small animals. However, there is concern over how regional availability of exogenously administered substrate may affect photon emission. We thus synthesized [125I]iodo-D-luciferin, which demonstrated substrate characteristics for firefly luciferase, and investigated its cell uptake kinetics and in vivo biodistribution. Luminescence assays of luc gene transduced cells confirmed a linear decline in emitted light units with decreasing luciferin concentration. Both luc gene transduced and control cells demonstrated a low level of cellular uptake and rapid washout of [125I]iodo-D-luciferin, although early uptake was slightly higher for transduced cells (P < 0.005). Biodistribution in ICR mice demonstrated that early uptakes in liver, lung, myocardium and muscle were lower with intraperitoneal compared to intravenous administration. In view of the poor cell uptake, uptake levels (< 3%ID/g) suggest that substrate concentration may limit light emission rates in organs such as bone, muscle, myocardium, and particularly the brain. Thus, substrate availability should be considered as a potential limiting factor for photon emission efficiency in certain organs when attempting quantitative interpretation of optical luc gene imaging.
Lee
K-H
KH
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Byun
S S
SS
Paik
J-Y
JY
Lee
S Y
SY
Song
S H
SH
Choe
Y S
YS
Kim
B-T
BT
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D049454:Firefly Luciferin / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling / Q000379:methods*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D009928:Organ Specificity; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; D049454:Firefly Luciferin; D008156:Luciferases