Henriksen G, Herz M, Hauser A, Schwaiger M, Wester H-J
Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Germany.
Nucl Med Biol. 2004 Oct;31(7):851-8. doi: 10.1016/j.nucmedbio.2004.05.004.
11C-labeled choline ([11C]CHO) and 18F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[18F]fluorocholine, ([18F]dOC), a non-metabolizable [18F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [18F]dOC was compared with that of [11C]choline ([11C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [18F]dOC and [11C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC50 [18F]dOC= 11 microM; IC50 [11C]CHO=13 microM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [18F]dOC after 5 min incubation time is comparable to that of [11C]CHO, whereas the uptake of [11C]CHO was superior after 20 min incubation time. As for [11C]CHO, kidney and liver were also the primary sites of uptake for [18F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [18F]dOC at 10 min post-injection, whereas [11C]CHO uptake was higher at later time points. In conclusion, [18F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [18F]dOC and [11C]CHO result in comparable cellular uptake levels at early time points. In contrast to [18F]dOC, which is transported but not intracellularly trapped, the choline kinase substrate [11C]CHO is transported into tumor cells and retained. Thus, the signal obtained by imaging early after injection is mainly reflecting transport, whereas a valid quantification of choline kinase activity needs imaging at later time points. Further studies have to clarify whether quantification of the transport capacity or the choline kinase activity result in a better pathophysiological correlate and thus is the more useful process for tumor characterization.
11C标记的胆碱（[11C]CHO）和18F氟化胆碱类似物已被证明是通过正电子发射断层扫描（PET）对肿瘤进行体内成像的有价值的示踪剂。本研究的目的是评估去羟基-[18F]氟胆碱（[18F]dOC），一种不可代谢的[18F]氟化胆碱类似物，是否可以作为能够被磷酸化的胆碱的替代物，从而仅通过靶向胆碱转运系统实现PET成像。在体外培养的大鼠胰腺癌和PC-3人前列腺癌细胞中，比较了[18F]dOC与[11C]胆碱（[11C]CHO）摄取的特异性。此外，在荷AR42J和PC-3肿瘤的小鼠中比较了[18F]dOC和[11C]CHO的生物分布。体外研究表明，相似浓度的冷胆碱可浓度依赖性地抑制这两种化合物的膜转运（[18F]dOC的IC50 = 11 microM；[11C]CHO的IC50 = 13 microM）。对PC-3和AR42J细胞的体外研究表明，孵育5分钟后[18F]dOC的内化部分与[11C]CHO相当，而孵育20分钟后[11C]CHO的摄取更优。与[11C]CHO一样，肾脏和肝脏也是[18F]dOC在体内摄取的主要部位。将两种示踪剂同时注射到荷AR42J肿瘤的小鼠中后，生物分布数据显示，注射后10分钟时[18F]dOC的肿瘤摄取略高，而在随后的时间点[11C]CHO的摄取更高。总之，[18F]dOC通过胆碱特异性转运系统被AR42J大鼠胰腺癌和PC-3人前列腺癌细胞摄取。[18F]dOC和[11C]CHO相似的转运速率导致早期时间点细胞摄取水平相当。与[18F]dOC不同，[18F]dOC被转运但未在细胞内滞留，胆碱激酶底物[11C]CHO被转运到肿瘤细胞并保留。因此，注射后早期成像获得的信号主要反映转运，而胆碱激酶活性的有效定量需要在稍后的时间点成像。进一步的研究必须阐明，对转运能力或胆碱激酶活性的定量是否能产生更好的病理生理相关性，从而成为更有用的肿瘤特征化过程。
