Lee K-H, Byun S S, Paik J-Y, Lee S Y, Song S H, Choe Y S, Kim B-T
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Nucl Med Commun. 2003 Sep;24(9):1003-9. doi: 10.1097/00006231-200309000-00009.
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.
光学荧光素酶基因成像正逐渐成为一种监测小动物基因表达的方法。然而，人们对外源性给予的底物在局部的可利用性如何影响光子发射存在担忧。因此，我们合成了[125I]碘代-D-荧光素，它表现出萤火虫荧光素酶的底物特性，并研究了其细胞摄取动力学和体内生物分布。对转导了luc基因的细胞进行发光测定证实，随着荧光素浓度降低，发射光单位呈线性下降。转导了luc基因的细胞和对照细胞对[125I]碘代-D-荧光素均表现出低水平的细胞摄取和快速清除，尽管转导细胞的早期摄取略高（P < 0.005）。ICR小鼠的生物分布表明，与静脉注射相比，腹腔注射时肝脏、肺、心肌和肌肉的早期摄取较低。鉴于细胞摄取较差，摄取水平（< 3%ID/g）表明底物浓度可能会限制骨骼、肌肉、心肌尤其是大脑等器官的发光速率。因此，在尝试对光学luc基因成像进行定量解释时，底物可利用性应被视为某些器官中光子发射效率的潜在限制因素。
