O-(2-[18F]Fluoroethyl)-L-tyrosine (FET):: a tracer for differentiation of tumour from inflammation in murine lymph nodes
O-(2-[18F]Fluoroethyl)-L-tyrosine (FET):: a tracer for differentiation of tumour from inflammation in murine lymph nodes
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DOI：
10.1007/s00259-002-0821-6
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发表时间：
2002-08-01
影响因子：
9.1
通讯作者：
Senekowitsch-Schmidtke, R
中科院分区：
文献类型：
--
作者：
Rau, FC;Weber, WA;Senekowitsch-Schmidtke, R
炎症细胞对[F-18]氟-2-脱氧-D-葡萄糖（FDG）的高摄取是正电子发射断层扫描（PET）淋巴结（LN）分期中假阳性结果的常见原因。以前的研究表明，放射性标记的氨基酸可能是比FDG更特异的肿瘤组织标记物。本研究的目的是定量研究FDG、[H-3]甲基-L-蛋氨酸（MET）和O-2-（[F-18]氟乙基）-L-酪氨酸（FET）在肿瘤浸润和免疫刺激的LN中的摄取。Balb/c和DBA/2小鼠的腘淋巴结通过向小鼠的右后足垫注射链脲佐菌素（STZ）（引起慢性淋巴结炎）或伴刀豆球蛋白A（Con A）（引起急性淋巴结炎）来刺激。通过将2 × 105个lacZ标记的T细胞小鼠淋巴瘤细胞接种到同基因小鼠的右后足垫中来诱导肿瘤浸润的腘淋巴结。在肿瘤细胞接种后21天或在STZ或Con A注射后的不同时间点，小鼠同时静脉内注射MET和FDG或MET和FET。30分钟后，处死小鼠并测定腘LN中的示踪剂摄取。未处理小鼠的外侧LN和LN作为对照。组织学和免疫组织化学分析表明，在STZ治疗的动物和急性炎症变化（嗜中性粒细胞的积累，血管扩张，滤泡增生）的慢性炎症（非特异性窦增生与巨噬细胞）的典型体征Con A治疗的动物。X-Gal染色证实了肿瘤接种小鼠注射侧LN中存在肿瘤细胞。在慢性淋巴结炎模型中，FDG摄取增加了3.0 +/- 0.1倍[从2.7 +/-0.2%注射剂量/克组织（%ID/g）增加到8.2 +/-1.2%注射剂量/克组织（%ID/g）]，MET摄取增加了2.0 +/- 0.01倍（从4.5 +/-0.6% ID/g增加到9.2 +/-1.1% ID/g）。在急性淋巴结炎模型中，FDG摄取增加3.9 +/- 0.3倍（从2.7 +/-0.2% ID/g增加至10.6 +/-2.4% ID/g），MET摄取增加1.9 +/- 0.1倍（从4.5 +/-0.6% ID/g增加至8.5 +/-1.4% ID/g）。相比之下，两种淋巴结炎模型中的FET摄取（1.0 +/- 0.03和1.2 +/- 0.04倍）与对照组无显著差异（分别为4.2 +/- 0.3至4.7 +/- 0.7和5.1 +/-0.4% ID/g）。所有三种示踪剂在肿瘤浸润淋巴结中的摄取均显著高于对照淋巴结。FDG摄取增加2.8 ± 0.15倍（从2.7 +/- 0.2至7.6 +/- 1.3%ID/g），MET摄取1.7 +/- 0.11倍（从4.5 +/- 0.6至7.5 +/-1.3% ID/g）和FET摄取2.4 0.15倍（从4.2 +/- 0.3至10.0 +/-1.8% ID/g）。炎性淋巴结的MET和FDG摄取与肿瘤浸润淋巴结相似或高于肿瘤浸润淋巴结（P=0.01和P
High uptake of [F-18]fluoro-2-deoxy-D-glucose (FDG) by inflammatory cells is a frequent cause of false positive results in lymph node (LN) staging by positron emission tomography. Previous studies suggest that radiolabelled amino acids may be more specific markers for viable tumour tissue than FDG. The aim of this study was to investigate quantitatively the uptake of FDG, [H-3]methyl-L-methionine (MET) and O-2-([F-18]fluoroethyl) -L-tyrosine (FET) in tumour-infiltrated and immunologically stimulated LNs. Popliteal LNs of Balb/c and DBA/2 mice were stimulated by injection into the right posterior foot pad of mice of either streptozotocin (STZ), causing chronic lymphadenitis, or concanavalin A (Con A), resulting in acute lymphadenitis. Tumour-infiltrated popliteal LNs were induced by inoculation of 2x10(5) lacZ-tagged T cell mouse lymphoma cells into the right Posterior foot pad of syngeneic mice. Twenty-one days post inoculation of tumour cells or at various time points after STZ or Con A injection, mice were simultaneously injected intravenously with MET and FDG or MET and FET. After 30 min, mice were sacrificed and tracer uptake was determined in popliteal LNs. Contralateral LNs and LNs of untreated mice served as controls. Histopathological and immunohistochemical analysis demonstrated typical signs of chronic inflammation (non-specific sinus hyperplasia with macrophages) in STZ-treated animals and acute inflammatory changes (accumulation of neutrophilic granulocytes, vascular dilation, follicular hyperplasia) in Con A-treated animals. X-Gal staining confirmed the presence of tumour cells in the LNs of the injected side of tumour-inoculated mice. In the chronic lymphadenitis model, FDG uptake increased 3.0 +/- 0.1 fold [from 2.7 +/- 0.2 to 8.2 +/- 1.2 percent of injected dose per gram tissue (%ID/g)] and MET uptake 2.0 +/- 0.01 fold (from 4.5 +/- 0.6 to 9.2 +/- 1.1 %ID/g). In the acute lymphadenitis model, FDG uptake increased 3.9 +/- 0.3 fold (from 2.7 +/- 0.2 to 10.6 +/- 2.4 %ID/g) and MET uptake 1.9 +/- 0.1 fold (from 4.5 +/- 0.6 to 8.5 +/- 1.4 %ID/g). In contrast, FET uptake in both lymphadenitis models (1.0 +/- 0.03 and 1.2 +/- 0.04 fold) was not significantly different from that in controls (from 4.2 +/- 0.3 to 4.7 +/- 0.7 and to 5.1 +/- 0.4 %ID/g, respectively). Uptake of all three tracers in tumour-infiltrated LNs was significantly higher than that in control LNs. FDG uptake increased 2.8 +/- 0.15 fold (from 2.7 +/- 0.2 to 7.6 +/- 1.3%ID/g), MET uptake 1.7 +/- 0.11 fold (from 4.5 +/- 0.6 to 7.5 +/- 1.3 %ID/g) and FET uptake 2.4 0.15 fold (from 4.2 +/- 0.3 to 10.0 +/- 1.8 %ID/g). MET and FDG uptake was similar or higher in inflammatory than in tumour-infiltrated LNs (P=0.01 and P