A novel facile method of labeling octreotide with (18)F-fluorine.
A novel facile method of labeling octreotide with (18)F-fluorine.
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DOI：
10.2967/jnumed.109.066902
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Boerman OC
中科院分区：
文献类型：
--
作者：
Laverman P;McBride WJ;Sharkey RM;Eek A;Joosten L;Oyen WJ;Goldenberg DM;Boerman OC
已经开发了几种用氟-18标记多肽的方法。然而，一般来说，这些都是费力的，需要多步合成。我们提出了一种基于NOTA(1，4，7-三氮杂环-1，4，7-三乙酸)与[18F]氟化铝(“Al18F”)络合的简便方法。该方法以18F标记NOTA-奥曲肽(IMP466)为特征。奥曲肽与NOTA络合物偶联，并用18F两步一锅法标记。根据标记缓冲液、多肽和铝浓度对标记程序进行了优化。测定放化产率、比活度、体外稳定性和受体亲和力。研究了18F-IMP466在AR42J荷瘤小鼠体内的生物分布，并与68Ga标记的IMP466进行了比较。此外，还获得了microPET/CT图像。用“Al18F”一步标记IMP466，产率为50%。用高效液相色谱法对标记产物进行纯化，去除游离的Al18F和未标记的多肽。放射性标记，包括纯化，在45min内完成。比活力为45000 GBq/mmo1，在37℃血清中稳定4h，在柠檬酸钠、醋酸钠、HEPES和MES缓冲液中，pH为4.1进行标记，在醋酸钠缓冲液中标记效果最佳。19F标记的IMP466对AR42J细胞的表观IC50为3.6 nM。2小时P.I.的生物分布研究肿瘤对18F-IMP466的摄取较高(28.3±5.2%ID/g，瘤血比：300±90)，过量的未标记多肽(8.6±0.7%ID/g)可阻断18F-IMP466的摄取，表明18F-IMP466在肿瘤中的蓄积是由受体介导的。68Ga-IMP466的生物分布与18F-IMP466相似。18F-IMP466在体内是稳定的，因为骨摄取仅为0.4±0.2%ID/g，而游离的“Al18F”在骨中迅速积累(在给药2 h时为36.9±5.0%ID/g)。MicroPET/CT扫描显示肿瘤显示良好，肿瘤内高度优先堆积。用两步一锅法可快速有效地用18F标记诺曲肽。该化合物体内稳定，在表达AR42J的SSTR2受体裸鼠体内生长迅速。该方法也可用于18F标记其他NOTA共轭化合物。
Several methods have been developed to label peptides with fluorine-18. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of [18F]aluminum fluoride (“Al18F”) by NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). The method is characterized by labeling NOTA-octreotide (IMP466) with 18F. Octreotide was conjugated with the NOTA chelate and was labeled with 18F in a two-step, one-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of 18F-IMP466 was studied in AR42J tumor-bearing mice and compared to that of 68Ga-labeled IMP466. In addition, microPET/CT images were acquired. IMP466 was labeled with “Al18F” in a single step with 50% yield. The labeled product was purified by HPLC to remove unbound “Al18F” and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol and the peptide was stable in serum for 4 h at 37° C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, HEPES and MES buffer and was optimal in sodium acetate buffer. The apparent IC50 of the 19F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h p.i. showed a high tumor uptake of 18F-IMP466 (28.3 ± 5.2 %ID/g, tumor-to-blood ratio: 300 ± 90), which could be blocked by an excess of unlabeled peptide (8.6 ± 0.7%ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of 68Ga-IMP466 was similar to that of 18F-IMP466. 18F-IMP466 was stable in vivo, since bone uptake was only 0.4 ± 0.2 %ID/g, whereas free “Al18F” accumulated rapidly in the bone (36.9 ± 5.0 %ID/g at 2 h p.i.). MicroPET/CT scans showed excellent tumor delineation and high preferential accumulation in the tumor. NOTA-octreotide could be labeled rapidly and efficiently with 18F using a two-step, one-pot, method. The compound was stable in vivo and showed rapid accretion in SSTR2-receptor expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds with 18F.
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影响因子：
7.3
作者：
Hausner, Sven H.;Marik, Jan;Gagnon, M. Karen J.;Sutcliffe, Julie L.
通讯作者：
Sutcliffe, Julie L.
DOI：
10.1007/s00259-009-1122-0
发表时间：
2009-09-01
影响因子：
9.1
作者：
Hultsch, Christina;Schottelius, Margret;Wester, Hans-Juergen
通讯作者：
Wester, Hans-Juergen
影响因子：
16.6
作者：
Mu, Linjing;Hoehne, Aileen;Klar, Ulrich
通讯作者：
Klar, Ulrich
影响因子：
1.8
作者：
Marik, Jan;Sutcliffe, Julie L.
通讯作者：
Sutcliffe, Julie L.
DOI：
10.1007/s00259-002-1012-1
发表时间：
2003-01-01
影响因子：
9.1
作者：
Wester, HJ;Schottelius, M;Schwaiger, M
通讯作者：
Schwaiger, M