PMID- 21186394
OWN - NLM
STAT- MEDLINE
DCOM- 20110419
LR  - 20110203
IS  - 1477-0539 (Electronic)
IS  - 1477-0520 (Linking)
VI  - 9
IP  - 4
DP  - 2011 Feb 21
TI  - Trifunctional 99mTc based radiopharmaceuticals: metal-mediated conjugation of a 
      peptide with a nucleus targeting intercalator.
PG  - 1071-8
LID - 10.1039/c0ob00504e [doi]
AB  - The development of molecular imaging agents with multiple functions has become a 
      major trend in radiopharmaceutical chemistry. We present herein the syntheses of 
      trifunctional compounds, combining an acridine orange (AO) based intercalator 
      with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated 
      conjugation of these two functions via the [2 + 1] approach to the third 
      function, the [M(CO)(3)](+) (M = (99m)Tc, Re) moiety, yielded the final 
      trifunctional molecules. The strongly fluorescent acridine orange, a nuclear 
      targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate 
      ligand and bombesin with an isonitrile group as a monodentate ligand. For cell 
      and nuclear uptake studies, [Re(L(1)-BBN)(L(2)-Ical)(CO)(3)] type complexes were 
      synthesized and characterized. For radiopharmaceutical purposes, the (99m)Tc 
      analogues have been prepared in a stepwise synthesis. Fluorescence microscopy 
      studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake 
      into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no 
      internalization was observed.
FAU - Zelenka, Karel
AU  - Zelenka K
AD  - Institute of Inorganic Chemistry, University of Zurich, Winterthurerstr. 190, 
      8057, Zurich, Switzerland.
FAU - Borsig, Lubor
AU  - Borsig L
FAU - Alberto, Roger
AU  - Alberto R
LA  - eng
PT  - Journal Article
DEP - 20101224
PL  - England
TA  - Org Biomol Chem
JT  - Organic & biomolecular chemistry
JID - 101154995
RN  - 0 (Ligands)
RN  - 0 (Peptides)
RN  - 0 (Radiopharmaceuticals)
RN  - 7440-26-8 (Technetium)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Nucleus/*chemistry/metabolism
MH  - Humans
MH  - Ligands
MH  - Mice
MH  - Molecular Structure
MH  - Peptides/*chemical synthesis/metabolism
MH  - Radiopharmaceuticals/*chemical synthesis
MH  - Technetium/*chemistry
EDAT- 2010/12/28 06:00
MHDA- 2011/04/20 06:00
CRDT- 2010/12/28 06:00
PHST- 2010/12/28 06:00 [entrez]
PHST- 2010/12/28 06:00 [pubmed]
PHST- 2011/04/20 06:00 [medline]
AID - 10.1039/c0ob00504e [doi]
PST - ppublish
SO  - Org Biomol Chem. 2011 Feb 21;9(4):1071-8. doi: 10.1039/c0ob00504e. Epub 2010 Dec 
      24.