High purity production and potential applications of copper-60 and copper-61
High purity production and potential applications of copper-60 and copper-61
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DOI：
10.1016/s0969-8051(98)00113-9
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发表时间：
1999-05-01
影响因子：
3.1
通讯作者：
Welch, MJ
中科院分区：
文献类型：
--
作者：
McCarthy, DW;Bass, LA;Welch, MJ
先前，我们描述了使用专门为低能量生物医学回旋加速器设计的靶系统的Cu-64的高产率生产。在这项研究中，使用这种目标系统的生产Cu-60和Cu-61的描述和这些同位素在标记生物分子的肿瘤和缺氧成像的效用被证明。Cu-60和Cu-61由Ni-60（p，n）Cu-60、Ni-61（p，n）Cu-61和Ni-60（d，n）Cu-61核反应产生。将镍靶（>99%富集或天然镍）镀在如前所述的金盘（54-225 μ m厚）上并照射（14.7MeV质子束和8.1MeV氘核束）。通过离子交换色谱法将铜同位素与镍分离，并通过伽马光谱法评估放射性同位素纯度。使用富集的Ni-60已经实现了高达865 mCi的Cu-60的产率。使用富集Ni-61生产Cu-61的最大产率为144 mCi，使用富集Ni-60生产Cu-61的最大产率为72 mCi。Cu-60的比活度（使用富集材料）为80至300 mCi/mug Cu，Cu-61的比活度为20至81 mCi/mug Cu。用质子和氘轰击天然镍靶，测定了产额和放射性同位素杂质，并与富集材料进行了比较。用Cu-60标记二乙酰基-双（N-4-甲基缩氨基硫脲）ATSM。将Cu-60-ATSM注射到具有闭塞的左前降支冠状动脉的大鼠中。Cu-60-ATSM在心脏的缺氧区域中的摄取使用放射自显影术清楚地可视化。此外，将Cu-60-ATSM注射到狗体内，并且使用正电子发射断层扫描（PET）获得了心脏和心壁的良好图像，Cu-61被标记为1，4，8，11-四氮杂环十四烷-N，N '，N“，N”“-四乙酸-奥曲肽（TETA-octreotide），并且获得了荷瘤大鼠的PET图像，直至注射后2 h。在Cu-61衰变后，向同一大鼠注射Cu-64-TETA-奥曲肽并比较图像。发现使用Cu-61获得的肿瘤图像上级使用Cu-64获得的肿瘤图像，如基于Cu-61相对于Cu-64发射的正电子的更大丰度所预测的，NUCL MED BIOL 26;4：351-358，1999。(C)1999 Elsevier Science Inc. All rights reserved.
Previously we described the high yield production of Cu-64 using a target system designed specifically for low energy, biomedical cyclotrons. In this study, the use of this target system for the production of Cu-60 and Cu-61 is described and the utility of these isotopes in the labeling of biomolecules for tumor and hypoxia imaging is demonstrated. Cu-60 and Cu-61 were produced by the Ni-60(p, n)Cu-60, Ni-61(p,n)Cu-61, and Ni-60(d,n)Cu-61 nuclear reactions. The nickel target (>99% enriched or natural nickel) was plated onto a gold disk as described previously (54-225 mu m thickness) and irradiated (14.7 MeV proton beam and 8.1 MeV deuteron beam). The copper isotopes were separated from the nickel via ion exchange chromatography and the radioisotopic purity was assessed by gamma spectroscopy. Yields of up to 865 mCi of Cu-60 have been achieved using enriched Ni-60. Cu-61 has been produced with a maximum yield of 144 mCi using enriched Ni-61 and 72 mCi using enriched Ni-60. Specific activities (using enriched material) ranged from 80 to 300 mCi/mu g Cu for Cu-60 and from 20 to 81 mCi/mu g Cu for Cu-61. Bombardments of natural Ni targets were performed using both protons and deuterons, Yields and radioisotopic impurities were determined and compared with that for enriched materials. Cu-60 was used to radiolabel diacetyl-bis(N-4-methylthiosemicarbazone), ATSM. Cu-60-ATSM was injected into rats that had an occluded left anterior descending coronary artery. Uptake of Cu-60-ATSM in the hypoxic region of the heart was visualized clearly using autoradiography. In addition, Cu-60-ATSM was injected into dogs and excellent images of the heart and heart walls were obtained using positron emission tomography (PET), Cu-61 was labeled to 1,4,8,11-tetraazacyclotetradecane-N,N',N ",N'''-tetraacetic acid-octreotide (TETA-octreotide) and the PET images of tumor-bearing rats were obtained up to 2 h postinjection. After decay of the Cu-61, the same rat was injected with Cu-64-TETA-octreotide and the images were compared. The tumor images obtained using Cu-61 were found to be superior to those using Cu-64 as predicted based on the larger abundance of positrons emitted by Cu-61 VS. Cu-64, NUCL MED BIOL 26;4:351-358, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.