CNN-Gd(3+) enables cell nucleus molecular imaging of prostate cancer cells: the last 600 nm.
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.
Heckl
Stefan
S
Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany. s.heckl@dkfz-heidelberg.de
Debus
Jürgen
J
Jenne
Jürgen
J
Pipkorn
Rüdiger
R
Waldeck
Waldemar
W
Spring
Herbert
H
Rastert
Ralf
R
von der Lieth
Claus W
CW
Braun
Klaus
K
D000595:Amino Acid Sequence; D051943:Antennapedia Homeodomain Protein; D002467:Cell Nucleus / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D051943:Antennapedia Homeodomain Protein; D003287:Contrast Media; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009942:Organometallic Compounds; D010446:Peptide Fragments; D014157:Transcription Factors; D005682:Gadolinium