Single amino acid chelates (SAAC): a strategy for the design of technetium and rhenium radiopharmaceuticals

Abstract

Radiolabeled biomolecules can be used to visualize a variety of diseases through interaction with specific cell receptors. A key step is the introduction of a molecular entity that allows facile labeling with the medically useful radionuclide (99m)Tc without significant alteration of the structure and function of the biomolecule. One strategy focuses on the design of single amino acid chelates (SAACs), novel bifunctional chelators constructed from derivatized amino acids or amino acid analogues. The chelating terminus of the SAAC has been designed for effective coordination to the {(99m)Tc(CO)(3)}(+) core, while the other terminus allows incorporation into any position along a peptide sequence or into a variety of biomolecules. In applications to peptidic materials, the approach affords significant flexibility in the choice of donors for (99m)Tc coordination combined with the considerable advantages of routine solid phase synthetic techniques. The methodology allows libraries of peptide-based (99m)Tc(i) and (186,188)Re(i) radiopharmaceuticals to prepared using conventional automated peptides synthesis. Other biomolecules, including nucleosides, carbohydrates, folic acid and vitamin B12 are also readily modified using analogous methods. The approach also allows the preparation of isostructural (99m)Tc and Re complexes for the correlation of in vivo and in vitro imaging studies.

fac‐[TcO3(tacn)]+: A Versatile Precursor for the Labelling of Pharmacophores, Amino Acids and Carbohydrates through a New Ligand‐Centred Labelling Strategy

“…To demonstrate the potential and flexibility of the [3+2] cycloaddition labelling concept, the Fmoc-protected 1-allyl-l-histidine, as a possible single amino acid chelate (SAAC) analogue, [29] and allyl 2,3,4,6-tetra-O-acetyl-b -(D)-glucopyranoside were synthesized and labelled with fac-{ 99m TcO 3 } + complexes ( [5] + and [7] + ; Scheme 1).…”

Metal-containing peptide nucleic acid conjugates

“…109 Tc has been the most commonly used radioisotope, probably due its ideal radio nuclear properties and the convenient availability from a commercial generator. [143][144][145][146] However, other radio-metals such as 64 Cu or 111 In have also been employed. Of interest for in vivo pharmacokinetics, our groups recently reported the biodistribution studies of a 12-mer PNA bioconjugate labeled with a tricarbonyl 99m Tc complex in Wistar rats.…”

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

“…Single amino-acids have been derivatized with luminescent Re(CO) 3 complexes in order to incorporate them into peptides, or to study their photophysical properties as such in cuvette or in a cellular context [22,43,90,[95][96][97]. Complexes 21 and 22 (Figure 10), for instance, have been appended with phenylalanine and tyrosine, and their photophysical properties were studied [95].…”

“…In most of these examples, the rhenium is used for its reactivity close to the technetium and for the similarities of the Re and Tc complexes. Moreover, as mentioned earlier, efforts are made to use the potential of Re(CO) 3 complexes as luminescent probes, and to develop isostructural nuclear and optical probes based on 99m Tc and Re, respectively [22,43,88,90,91]. In addition, 186 Re and 188 Re isotopes can be used for radiotherapy, and 186/188 Re tricarbonyl complexes have been designed for that purpose [92][93][94].…”

“…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].…”