CNN-Gd(3+) enables cell nucleus molecular imaging of prostate cancer cells: the last 600 nm

Cancer Res. 2002 Dec 1;62(23):7018-24.

Abstract

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 (Gd(3+)) with a cell-nucleus directed peptide module could be helpful. This modular molecule is characterized by a Gd(3+)-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 Gd(3+)-complex (CNN-Gd(3+)-complex). By use of magnetic resonance imaging, Gd(3+) 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.

MeSH terms

  • Amino Acid Sequence
  • Antennapedia Homeodomain Protein
  • Cell Nucleus / metabolism
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics*
  • Gadolinium / chemistry
  • Gadolinium / pharmacokinetics*
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / pharmacokinetics*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / pharmacokinetics*
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics*
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacokinetics*
  • Prostatic Neoplasms / metabolism*
  • Protein Transport / physiology
  • Sequence Homology, Amino Acid
  • Transcription Factors*

Substances

  • Antennapedia Homeodomain Protein
  • Contrast Media
  • Homeodomain Proteins
  • Nuclear Proteins
  • Organometallic Compounds
  • Peptide Fragments
  • Transcription Factors
  • Gadolinium