Chelating Systems for 99mTc/188Re in the Development of Radiolabeled Peptide Pharmaceuticals

Abstract

Currently, receptor based radiopharmaceuticals have received great attention in molecular imaging and radiotherapy of cancer, and provide a unique tool for target-specific delivery of radionuclides to pathological tissues. In this context, receptor binding peptides represent an attractive class of target vectors for Nuclear Medicine purposes. The rich chemistry of the group 7 elements elaborated in past years, has allowed the development of different procedures for the preparation of radiolabeled peptides in high yield. This, joint to the use of solid-phase peptide synthesis, has opened the possibility to explore new strategies for approaching the design of new class of radiolabeled receptor-targeted peptides, and to create new versatilities in targeting vehicle design e.g. in synthesis of metal-cyclized peptides or of multivalent targeting agents. This review provides an overview on several aspects of the development of new (99m)Tc/(188)Re-peptide based target specific radiopharmaceuticals, in particular on the synthetic strategies employed for modifying molecular vectors, and the application of the different metal-cores and/or building block for preparing high specific activity agents.

ReVO and ReVNPh complexes with pentadentate benzamidines – Synthesis, structural characterization and DFT evaluation of isomeric complexes

“…Beside several other applications, rhenium compounds currently attract interest because of potential applications of complexes of the isotopes 186 Re and 188 Re in radiotherapy [1][2][3][4][5][6].…”

Synthesis, Characterization, and Binding to the Translocator Protein (18 kDa, TSPO) of a New Rhenium Complex as a Model of Radiopharmaceutical Agents

“…Technetium and rhenium have very similar chemistry that enables the same experimental conditions to be applied to the preparation of radiopharmaceuticals for diagnostic ( 99m Tc) and therapeutic applications ( 186/188 Re) in nuclear medicine 24. Therefore, nonradioactive rhenium complexes are often used as model compounds for the 99m Tc congeners 25–30. Technetium and rhenium offer also the possibility of exploring a large variety of oxidation states in relation to different types of ligands and bifunctional and trifunctional chelators 31–34.…”

Optimizing Labeling Conditions for Cysteine-Based Peptides with99mTc

“…Substitution of the amino acids forming the chelator for binding 99m Tc effected on the biodistribution of affibody molecules. [20][21][22][23][24] Our efforts were focused on radiolabeling of LTVSPWY peptide with 99m Tc by two cycteine-based ligands of Cys-Gly-Gly-Gly and Cys-Ser-Ser-Ser. 99m Tc radiolabeling of two peptides were accomplished through direct reduction and ligand exchange methods.…”