Bridging the gap between in vitro and in vivo imaging: isostructural Re and 99mTc complexes for correlating fluorescence and radioimaging studies.
A bifunctional ligand that is capable of forming Re and 99mTc complexes as complementary fluorescent and radioactive probes was developed. The tridentate bis(quinoline) amine ligand, which is referred to as the SAACQ system, was prepared in a single step from Fmoc protected lysine in high yield. Reaction of the SAACQ ligand with [Re(CO)3Br3]2- resulted in the formation of the SAACQ-(Re(CO)3)+complex which exhibits favorable fluorescence properties including a long lifetime and a large Stoke's shift. Because the SAACQ ligand is derived from an amino acid, it can readily be linked to or incorporated within peptides as a means of targeting the probe to specific receptors. To demonstrate this feature, the SAACQ ligand and the SAACQ-Re complex were incorporated into fMLFG, a peptide that binds to the formyl peptide receptor (FPR). Uptake of the fMLF[(SAACQ-Re(CO)3)+]G conjugate into human leukocytes in vitro was visualized by fluorescence microscopy, and the observed distribution of the peptide was similar to that of a well-established fluorescent FPR probe. The corresponding Tc complex, fMLF[(SAACQ-99mTc(CO)3)+]G, was prepared in excellent yield from [99mTc(CO)3(OH2)3]+, which affords the opportunity to correlate the results of the microscopy experiments with in vivo radioimaging studies because the probes are isostructural.
Stephenson
Karin A
KA
Department of Chemistry, McMaster University, Hamilton, Ontario, Canada L8S 4M1.
Banerjee
Sangeeta Ray
SR
Besanger
Travis
T
Sogbein
Oyebola O
OO
Levadala
Murali K
MK
McFarlane
Nicole
N
Lemon
Jennifer A
JA
Boreham
Douglas R
DR
Maresca
Kevin P
KP
Brennan
John D
JD
Babich
John W
JW
Zubieta
Jon
J
Valliant
John F
JF
D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008024:Ligands; D008856:Microscopy, Fluorescence / Q000379:methods; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*
D005456:Fluorescent Dyes; D008024:Ligands; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium