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CNN-Gd³⁺ Enables Cell Nucleus Molecular Imaging of Prostate Cancer Cells: The Last 600 nm

Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany [S. H.]; Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center, Heidelberg, Germany [J. D., J. J., R. R., K. B.]; Central Section for Peptide Synthesis, German Cancer Research Center, Heidelberg, Germany [R. P.]; Division Organisation of Complex Genomes, German Cancer Research Center, Heidelberg, Germany [H. S.]; Division Biophysics of Macromolecules, German Cancer Research Center, Heidelberg, Germany [W. W.]; and Central Section for Spectroscopy, German Cancer Research Center, Heidelberg, Germany [C. W. v. d. L.]

Molecular imaging is defined as the characterization and measurement of biological processes at the cellular and molecular level. Molecular imaging, therefore, necessitates a sufficient amount of contrast agent within the cell. Consequently, we realized that the intracellular uptake and cell compartment specificity of the commonly used interstitial contrast agent gadolinium (Gd³⁺) with a cell-nucleus directed peptide module could be helpful. This modular molecule is characterized by a Gd³⁺-complex module that is bound to a transmembrane transport unit (TPU) of human origin and further to a nucleus-directed address module (nuclear localization sequence) resulting in a specific cell nucleus-directed nuclear localization sequence-conjugated Gd³⁺-complex (CNN-Gd³⁺-complex). By use of magnetic resonance imaging, Gd³⁺ was detected within DU-145 prostate cancer cells after only 10 min. The nuclear localization was confirmed with confocal laser scanning microscopy. The resulting MRI signal enhancement only slightly decreased over the next 48 h compared with an absolute loss of signal enhancement after only 8 h when a random target sequence was used. Therefore, our method seems promising for in vivo application in molecular imaging.

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