TY - JOUR T1 - Nuclear Uptake and Dosimetry of <sup>64</sup>Cu-Labeled Chelator–Somatostatin Conjugates in an SSTr2-Transfected Human Tumor Cell Line JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1390 LP - 1396 DO - 10.2967/jnumed.107.039990 VL - 48 IS - 8 AU - Martin Eiblmaier AU - Rebecca Andrews AU - Richard Laforest AU - Buck E. Rogers AU - Carolyn J. Anderson Y1 - 2007/08/01 UR - http://jnm.snmjournals.org/content/48/8/1390.abstract N2 - 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 (&gt;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 &lt;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. ER -