Bridging the Gap between in Vitro and in Vivo Imaging:  Isostructural Re and^99mTc Complexes for Correlating Fluorescence and Radioimaging Studies

Abstract

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.

Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology

“…Two families of ligand have been particularly explored: (i) polypyridyl ligands, mostly derived from 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) [19][20][21][23][24][25][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and (ii) bis-quinoline and its derivatives, e.g. bis(phenanthridinylmethyl)amine (bpm) [22,[43][44][45]. However, other polyazaheterocycles have also been developed, such as 1-R-4-(2-pyridyl)-1,2,3-triazole (pyta) and its derivatives [46][47][48].…”

Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe

“…These results concur with previous reports from microscopy studies of other fluorescentlylabeled chemotactic peptides. 22,[45][46][47] By establishing a linear correlation between the fluorescence intensity and the neutrophil concentration, it was demonstrated that the nanoprobe may have some potential for quantitative analysis of neutrophils in vivo. 25 Subcutaneous injection of LPS is a well-established inflammation model prompting severe inflammatory responses, accompanied by the recruitment of neutrophils, macrophages/monocytes, and other immune cells.…”

A Bridge Not Too Far: Linking Disciplines Through Molecular Imaging Probes

“…Our group reported the development of a chelate system whereby the nonradioactive rhenium complex was fluorescent (63). The 99m Tc analog, because of the lanthanide contraction, has the same structure as the rhenium complex and can be used for in vivo imaging.…”