New Bifunctional Chelator for 64Cu-Immuno-Positron Emission Tomography

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• 作者：Darpan N. Pandya ; Nikunj Bhatt ; Ajit V. Dale ; Jung Young Kim ; Hochun Lee ; Yeong Su Ha ; Ji-Eun Lee ; Gwang Il An ; Jeongsoo Yoo
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：August 21, 2013
• 年：2013
• 卷：24
• 期：8
• 页码：1356-1366
• 全文大小：462K
• 年卷期：v.24,no.8(August 21, 2013)
• ISSN：1520-4812

文摘

A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH₂ complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with ⁶⁴Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the ⁶⁴Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by ⁶⁴Cu-immuno-positron emission tomography imaging in animal models.