Optimized labeling of NOTA-conjugated octreotide with F-18.
Optimized labeling of NOTA-conjugated octreotide with F-18.
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DOI：
10.1007/s13277-011-0250-x
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Boerman, Otto C.
中科院分区：
文献类型：
--
作者：
Laverman, Peter;D'Souza, Christopher A.;Eek, Annemarie;McBride, William J.;Sharkey, Robert M.;Oyen, Wim J. G.;Goldenberg, David M.;Boerman, Otto C.
我们最近报道了一种基于NOTA（1,4,7-三氮杂环壬烷-1,4,7-三乙酸）螯合[18F]氟化铝（Al18F）的简便方法。本文对NOTA-octreotide （IMP466）的18F标记进行了进一步优化。奥曲肽与NOTA螯合物偶联，用18F标记，两步，一锅法。根据标记缓冲液、离子强度、肽浓度和温度对标记过程进行了优化。测定了放射线化学产率、比活性、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。此外，还采集了显微pet /CT图像。在80% （v/v）乙腈或乙醇存在下，用Al18F单步标记IMP466，收率为97%。用高效液相色谱法纯化标记产物，去除未标记的肽和未结合的Al18F。放射性标记，包括纯化，进行45分钟。比活性为48000 GBq/mmol。18F-IMP466在注射后2小时显示出高的肿瘤摄取和良好的肿瘤与血液比率。此外，低骨摄取表明Al18F-NOTA复合物在体内是稳定的。PET/CT扫描显示良好的肿瘤描绘和肿瘤内特异性堆积。受体阴性器官的摄取较低。NOTA-octreotide可以用18F标记，采用快速两步一锅法定量产率。该化合物在体内稳定，并在裸鼠表达sstr2受体的AR42J肿瘤中迅速增殖。该方法可用于标记其他nota偶联化合物，如RGD肽、grpr结合肽和18F的粘附体分子。
We recently reported a facile method based on the chelation of [18F]aluminum fluoride (Al18F) by NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). Here, we present a further optimization of the 18F labeling of NOTA-octreotide (IMP466). 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, ionic strength, peptide concentration, and temperature. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of 18F-IMP466 was studied in AR42J tumor-bearing mice. In addition, microPET/CT images were acquired. IMP466 was labeled with Al18F in a single step with 97% yield in the presence of 80% (v/v) acetonitrile or ethanol. The labeled product was purified by HPLC to remove unlabeled peptide and unbound Al18F. The radiolabeling, including purification, was performed for 45 min. Specific activities of 48,000 GBq/mmol could be obtained. 18F-IMP466 showed a high tumor uptake and excellent tumor-to-blood ratios at 2 h post-injection. In addition, the low bone uptake indicated that the Al18F–NOTA complex was stable in vivo. PET/CT scans revealed excellent tumor delineation and specific accumulation in the tumor. Uptake in receptor-negative organs was low. NOTA-octreotide could be labeled with 18F in quantitative yields using a rapid 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 such as RGD peptides, GRPR-binding peptides, and Affibody molecules 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：
3.9
作者：
RAJAN, KS;MAINER, S;DAVIS, JM
通讯作者：
DAVIS, JM
DOI：
10.2967/jnumed.109.066902
发表时间：
2010-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Laverman P;McBride WJ;Sharkey RM;Eek A;Joosten L;Oyen WJ;Goldenberg DM;Boerman OC
通讯作者：
Boerman OC
影响因子：
16.6
作者：
Mu, Linjing;Hoehne, Aileen;Klar, Ulrich
通讯作者：
Klar, Ulrich