New lyophilized kit for rapid radiofluorination of peptides.
New lyophilized kit for rapid radiofluorination of peptides.
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DOI：
10.1021/bc200608e
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发表时间：
2012-03-21
影响因子：
4.7
通讯作者：
Goldenberg, David M.
中科院分区：
文献类型：
--
作者：
McBride, William J.;D'Souza, Christopher A.;Karacay, Habibe;Sharkey, Robert M.;Goldenberg, David M.
用发射正电子的放射性核素对化合物进行放射性标记通常涉及耗时的定制过程。在此，我们报告了一个简单的冻干试剂盒配方标记肽与18F，氟化铝程序的基础上。原型套件包含IMP 485，一种NODA（1，4，7-三氮杂环壬烷-1，4-二乙酸酯）-MPAA（甲基苯乙酸）-di-HSG（组胺-琥珀酰-甘氨酸）半抗原-肽[NODA-MPAA-D-Lys（HSG）-D-Tyr-D-Lys（HSG）-NH 2]，用于预靶向，但我们也检查了生长抑素结合肽[IMP 466，NOTA-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Throl]，以确定使用试剂盒的益处是否可以扩展到其他AlF结合肽。NODA-MPAA配体与（AlF）2+以高产率形成单一稳定的复合物。为了建立用于简易试剂盒的合适条件，针对pH、肽与Al 3+比率、填充剂、辐射防护剂和缓冲液对制剂进行了优化。为了实现最佳标记，试剂盒用18F−和乙醇（1：1）的水溶液复溶，在100-110 °C下加热15分钟，然后使用两种同样有效的固相萃取（SPE）方法之一简单快速地纯化。Al 18F-IMP 485在20 min内以单一异构体复合物形式分离，产率高（45-97%），比活度高（高达223 GBq/μmol）。标记产物在人血清中37 °C下稳定4 h，体内尿样显示完整产物被消除。在携带用抗CEACAM 5双特异性抗体预靶向的人结肠癌异种移植物的裸鼠中Al 18F-IMP 485的肿瘤靶向在骨中显示非常低的摄取（0.06% ± 0.02ID/g），进一步说明其稳定性。在1小时时，预先靶向的动物具有高Al 18F-IMP 485肿瘤摄取（28.1% ± 4.5ID/g），肾脏、肝脏、血液和骨骼的比率分别为9 ± 4、123 ± 38、110 ± 43和120 ± 108。肿瘤摄取在注射后3小时保持高水平，肿瘤/非肿瘤比率增加。NOTA-生长抑素结合肽也被氟化，在相同的试剂盒制剂中具有良好的产率和高比活性。然而，产率略低于用含有NODA-MPAA配体的IMP 485实现的产率，可能反映了该配体优于简单NOTA的上级结合性质。这些研究表明，18F-标记的肽可以重复地制备为稳定的Al-F复合物，具有良好的放射化学产率和高比活性，使用简单的一步冻干试剂盒，然后通过SPE快速纯化，提供18F-肽，准备在30分钟内注射给患者。
Radiolabeling compounds with positron-emitting radionuclides often involves a time-consuming, customized process. Herein, we report a simple lyophilized kit formulation for labeling peptides with 18F, based on the aluminum-fluoride procedure. The prototype kit contains IMP485, a NODA (1,4,7-triazacyclononane-1,4-diacetate)-MPAA (methyl phenylacetic acid)-di-HSG (histamine-succinyl-glycine) hapten-peptide, [NODA-MPAA-D-Lys(HSG)-D-Tyr-D-Lys(HSG)-NH2], used for pretargeting, but we also examined a similar kit formulation for a somatostatin-binding peptide [IMP466, NOTA-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Throl] bearing a NOTA ligand to determine if the benefits of using a kit can be extended to other AlF-binding peptides. The NODA-MPAA ligand forms a single stable complex with (AlF)2+ in high yields. In order to establish suitable conditions for a facile kit, the formulation was optimized for pH, peptide to Al3+ ratio, bulking agent, radioprotectant, and the buffer. For optimal labeling, the kit was reconstituted with an aqueous solution of 18F− and ethanol (1:1), heated at 100–110 °C for 15 min, and then simply and rapidly purified using one of two equally effective solid-phase extraction (SPE) methods. Al18F-IMP485 was isolated as a single isomer complex, in high yield (45–97%) and high specific activity (up to 223 GBq/μmol), within 20 min. The labeled product was stable in human serum at 37 °C for 4 h and in vivo, urine samples showed the intact product was eliminated. Tumor targeting of the Al18F-IMP485 in nude mice bearing human colon cancer xenografts pretargeted with an anti-CEACAM5 bispecific antibody showed very low uptake (0.06% ± 0.02 ID/g) in bone, further illustrating its stability. At 1 h, pretargeted animals had high Al18F-IMP485 tumor uptake (28.1% ± 4.5 ID/g), with ratios of 9 ± 4, 123 ± 38, 110 ± 43 and 120 ± 108 for kidney, liver, blood and bone, respectively. Tumor uptake remained high at 3 h post-injection, with increased tumor/nontumor ratios. The NOTA-somatostatin-binding peptide also was fluorinated with good yield and high specific activity in the same kit formulation. However, yields were somewhat lower than those achieved with IMP485 containing the NODA-MPAA ligand, likely reflecting this ligand's superior binding properties over the simple NOTA. These studies indicate that 18F-labeled peptides can be reproducibly prepared as stable Al-F complexes with good radiochemical yield and high specific activity using a simple, one-step, lyophilized kit followed by a rapid purification by SPE that provides the 18F-peptide, ready for patient injection within 30 min.
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DOI：
10.1073/pnas.0600982103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Rossi, EA;Goldenberg, DM;Chang, CH
通讯作者：
Chang, CH
影响因子：
4.7
作者：
Lang, Lixin;Li, Weihua;Guo, Ning;Ma, Ying;Zhu, Lei;Kiesewetter, Dale O.;Shen, Baozhong;Niu, Gang;Chen, Xiaoyuan
通讯作者：
Chen, Xiaoyuan
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
使用 64Cu- 和 68Ga-Somatostatin 拮抗剂对生长抑素受体阳性肿瘤进行 PET 研究： 螯合物的作用
影响因子：
9.3
作者：
Fani, Melpomeni;Del Pozzo, Luigi;Maecke, Helmut R.
通讯作者：
Maecke, Helmut R.
影响因子：
1.8
作者：
Marik, Jan;Sutcliffe, Julie L.
通讯作者：
Sutcliffe, Julie L.