Nuclear Uptake and Dosimetry of 64Cu-Labeled Chelator–Somatostatin Conjugates in an SSTr2-Transfected Human Tumor Cell Line

Journal of Nuclear Medicine

Martin Eiblmaier¹  Rebecca Andrews¹  Carolyn J. Anderson¹  Richard Laforest¹  Buck E. Rogers¹ 

关键词: ⁶⁴Cu;    targeted radiotherapy;    somatostatin receptor;    somatostatin analog;    dosimetry;   

DOI  :  10.2967/jnumed.107.039990

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

64Cu radiopharmaceuticals have shown tumor growth inhibition in tumor-bearing animal models with a relatively low radiation dose that may be related to nuclear localization of the 64Cu in tumor cells. Here we address whether the nuclear localization of 64Cu from a 64Cu-labeled chelator–somatostatin conjugate is related to the dissociation of the radio-copper from its chelator. The 64Cu complex of 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA) has demonstrated instability in vivo, whereas 64Cu-CB-TE2A (CB-TE2A is 4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) was highly stable. Methods: Receptor binding, nuclear uptake, internalization, and efflux assays were performed to characterize the interaction with the somatostatin receptor and the intracellular fate of 64Cu-labeled chelator–peptide conjugates in A427-7 cells. From these data, the absorbed dose to cells was calculated. Results: 64Cu-TETA-Y3-TATE (64Cu-[1]) and 64Cu-CB-TE2A-Y3-TATE (64Cu-[2]) had high affinity for somatostatin receptor subtype 2 (SSTr2) in A427-7 cells. After 3 h, 64Cu-[2] showed greater internalization (>30%) compared with 64Cu-[1] (∼15%). There was uptake of 64Cu-[1] in nuclei of 427–7 cells (9.4% ± 1.7% at 24 h), whereas 64Cu-[2] showed minimal nuclear accumulation out to 24 h (1.3% ± 0.1%). A427-7 cells were exposed to 0.40 Gy from 64Cu-[1] and exposed to 1.06 Gy from 64Cu-[2]. External beam irradiation of A427-7 cells showed <20% cell killing at 1 Gy. Conclusion: These results are consistent with our hypothesis that dissociation of 64Cu from TETA leads to nuclear localization. Dosimetry calculations indicated that the nuclear localization of 64Cu-[1] was not significant enough to increase the absorbed dose to the nuclei of A427-7 cells. These studies show that 64Cu localization to cell nuclei from internalizing, receptor-targeted radiopharmaceuticals is related to chelate stability.

【 授权许可】

Unknown