Wester H J, Schottelius M, Scheidhauer K, Meisetschläger G, Herz M, Rau F C, Reubi J C, Schwaiger M
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 München, Germany.
Eur J Nucl Med Mol Imaging. 2003 Jan;30(1):117-22. doi: 10.1007/s00259-002-1012-1. Epub 2002 Nov 5.
Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin receptor (sst) scintigraphy with PET, a novel carbohydrated (18)F-labelled sst ligand was developed and preclinically evaluated. Synthesis of N(alpha)-(1-deoxy- D-fructosyl)- N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate ([(18)F]FP-Gluc-TOCA) was completed in approximately 3 h (20%-30% yield). [(19)F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC(50): 437+/-84 n M) and hsst5 (IC(50): 123+/-8.8 n M) and very high affinity to hsst2 (IC(50): 2.8+/-0.4 n M). As a result of carbohydration, lipophilicity of [(18)F]FP-Gluc-TOCA was found to be low (lg P(OW)=-1.70+/-0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%+/-1.09%ID/g) and showed low uptake in liver (0.72%+/-0.14%ID/g) and intestine (1.88%+/-0.52%ID/g) and high tumour uptake (13.54%+/-1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, respectively. A similar biodistribution pattern was observed in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 microg Tyr(3)-octreotide, demonstrating sst-specific uptake. In a first [(18)F]FP-Gluc-TOCA-PET study of a patient with a metastatic carcinoid in the liver the tracer showed superior pharmacokinetics, e.g. rapid urinary excretion and low uptake in liver, kidney and spleen. Multiple liver lesions (SUVs ranging from 21.4 to 38.0) and previously unknown focal uptake in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an (18)F-labelled sst binding peptide; it indicates that [(18)F]FP-Gluc-TOCA offers excellent imaging characteristics and allows sst imaging with high tumour to non-tumour contrast.
由于氟 - 18具有出色的核性质，以及对正电子发射断层扫描（PET）的生长抑素受体（sst）闪烁扫描的兴趣日益增加，一种新型的碳水化合物标记的（18）F标记的sst配体被开发并进行了临床前评估。N（α） - （1 - 脱氧 - D - 果糖基） - N（ε） - （2 - [（18）F]氟丙酰基） - Lys（0） - Tyr（3） - 奥曲肽（[（18）F] FP - Gluc - TOCA）的合成在约3小时内完成（产率20% - 30%）。[（19）F] FP - Gluc - TOCA对hsstl和hsst3无亲和力，对hsst4（IC50：437±84 nM）和hsst5（IC50：123±8.8 nM）具有中等亲和力，对hsst2（IC50：2.8±0.4 nM）具有非常高的亲和力。由于碳水化合物化，发现[（18）F] FP - Gluc - TOCA的亲脂性较低（lg P（OW）=-1.70±0.02）。在小鼠中，该示踪剂通过肾脏排泄迅速清除（肾脏：8.69%±1.09%ID/g），在肝脏（0.72%±0.14%ID/g）和肠道（1.88%±0.52%ID/g）中摄取较低，在肿瘤中摄取较高（13.54%±1.47%ID/g）（所有数据均在注射后1小时）。注射后60分钟时，肿瘤与非肿瘤的比值在血液、肝脏、肠道、肾脏和肌肉中分别达到25、19、7、1.6和56。在荷胰腺肿瘤的大鼠中观察到类似的生物分布模式。通过共同注射500μg Tyr（3） - 奥曲肽，大鼠的肿瘤摄取在对照（30和60分钟）时分别降至36%和18%，表明是sst特异性摄取。在对一名肝脏转移性类癌患者进行的首次[（18）F] FP - Gluc - TOCA - PET研究中，该示踪剂显示出优异的药代动力学，例如快速的尿液排泄以及在肝脏、肾脏和脾脏中的低摄取。多个肝脏病变（SUV范围为21.4至38.0）和腹部先前未知的局灶性摄取（SUV 10.0）清晰可见。这是关于使用（18）F标记的sst结合肽进行PET成像的首次报告；它表明[（18）F] FP - Gluc - TOCA具有出色的成像特性，并允许以高肿瘤与非肿瘤对比度进行sst成像。
