Impact of functionalized coligands on the pharmacokinetics of 99mTc(III) ‘4+1’ mixed-ligand complexes conjugated to bombesin

Organometallic–Peptide Bioconjugates: Synthetic Strategies and Medicinal Applications

“…Using an isocyanide-functionalized N-terminus, Pietzsch and Kozminski and co-workers 178−182 showed that a metal−carbon bond is formed between the coordination complex and the peptide, resulting in a lipophilic 4 + 1 (or κ 1 on the side of the peptide) mixed-ligand complex (Chart 5, generic structure 40). 183 In recent years, these OM−peptide conjugates have been successfully applied in tumor-imaging strategies 184 and have proven to be significantly stable to allow biological tests. 179 Using the mixed-ligand framework of these OM−peptide conjugates, hydrophilic coligands were introduced (41 and 42, Chart 5), which shifted the excretion of these conjugates from hepatobiliary to an equal rate of renal and hepatobiliary pathways, thus improving the in vivo properties.…”

“…An alternative multistep strategy for the labeling of peptides with 99m Tc or Re coordination complexes uses an N-terminally positioned electron-rich carbon atom as a donor group, resulting in organometallic–peptide conjugates. Using an isocyanide-functionalized N-terminus, Pietzsch and Kozminski and co-workers − showed that a metal–carbon bond is formed between the coordination complex and the peptide, resulting in a lipophilic 4 + 1 (or κ 1 on the side of the peptide) mixed-ligand complex (Chart , generic structure 40 ) . In recent years, these OM–peptide conjugates have been successfully applied in tumor-imaging strategies and have proven to be significantly stable to allow biological tests .…”

“… a The basic core of the OM–peptide conjugate is shown, as well as two examples in which the lipophilic nature of the 4 + 1 complex was suppressed. These OM–peptide conjugates can be prepared in the presence of several peptidyl functional groups, as is apparent from the structures of the peptides that have been successfully used. − . M = 99m Tc I or Re I . …”

Organometallic Complexes for SPECT Imaging and/or Radionuclide Therapy

“…The building blocks [M(NS 3 )(CNR)] (M = Tc, Re) correspond to mixed-ligand Tc(III)/Re(III) complexes containing the umbrella type ligand 2,2′,2″-nitrilotris(ethanethiol) (NS 3 ) and isocyanides (CNR) as coligands, which preferably can carry biomolecules. A variety of biomolecules (e.g., central nervous system receptor ligands, peptides, and fatty acids) have been labeled with these building blocks within the so-called [4 + 1] mixed-ligand concept. − At the macroscopic level, the building blocks [Re(NS 3 )(CNR)] ( 13 ) were prepared by substitution of the phosphine ligand in [Re(NS 3 )(PR 3 )] ( 12 ) by an isocyanide (Scheme ). , X-ray structural analyses of some of these [4 + 1] complexes confirmed that the metal is pentacoordinate with a nearly ideal trigonal-bipyramidal geometry. The trigonal plane is defined by the three sulfur atoms of the NS 3 ligand, while the central nitrogen atom from the same ligand and the monodentate isocyanides occupy the apical positions.…”

Inorganic pharmaceuticals

“…Imaging applications were reported for bombesins-containing 99m Tc '4 + 1' complexes that are useful to detect tumours expressing the gastrin-releasing peptide receptor, 6 along with 99m Tc(CO) 3 -labeled pamidronate and alendronate for bone imaging, 7 and the first examples of 99m Tc bioconjugates that combine specific cell targeting with nuclear internalisation, a crucial issue to explore use of 99m Tc in Auger therapy. 154…”