99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Abstract

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99m Tc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the "in vitro" and "in vivo" behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes' molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [ 18 F]Fluoromisonidazole (FMISO) is also presented.

Development and Evaluation of 99mTc Tricarbonyl Complexes Derived from Flutamide with Affinity for Androgen Receptor

“…When compared with flutamide, which has a high PPB (95 ± 1%), all the complexes presented clearly lower values. These results show the impact of the donor atoms set on the overall physicochemical behavior of Tc-labeled small biomolecules, a fact that has been corroborated by our group and other research groups before [ 14 , 15 , 17 ]. A comparison of C3 , which has the lowest PPB, with C4 , which has the highest value, also demonstrates that the length of the linker has, as expected, a considerable impact on the physicochemical properties of the labeled compounds.…”

“…Even if these early attempts to prepare 99m Tc-labeled derivatives were not successful, further research should be undertaken since the influences of the chelator and spacer in the biological properties of potential radiopharmaceuticals are well documented in the literature for a variety of molecular targets [ 12 , 13 , 14 , 15 , 16 ].…”

Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein

“…99m Tc has been the most widely used SPECT isotope due to its in-house availability and reasonable cost, and it possesses ideal nuclide properties (t 1/2 = 6 h, E g =140 keV), as well as rich coordination chemistry with various oxidation states and donor atom sets. 20 In 2020, Lindner et al reported several 99m Tc-labeled FAPI radiotracers, 21 and 99m Tc-FAPI-34 with high affinity and significant tumor uptake was applied for preclinical models and SPECT of patients with metastasized ovarian and pancreatic cancer. In addition, the therapeutic use of 188 Re of this agent is attractive.…”

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

“…Nitroimidazole is the most widely used pharmacophore for hypoxia imaging because it can differentiate hypoxic and normoxic tissue. The potential for targeting hypoxia mostly depends on the single-electron reduction potential (SERP); the more positive the SERP value of a nitroimidazole is, the better its reduction potential of enzymes in aerobic cells [ 25 ]. Therefore, 2-nitroimidazole with the highest SERP value has become the most popular pharmacophore for the development of hypoxia probes compared with 4-nitroimidazole and 5-nitroimidazole.…”

“…Technetium-99m has been the most widely used SPECT isotope because it possesses ideal nuclide properties ( t 1/2 = 6 h, Eg = 140 keV) and rich coordination chemistry with various oxidation states and donor atom sets [ 25 ]. In addition, its in-house availability and reasonable cost have resulted in wide clinical use, especially in many developing countries and less-developed regions [ 13 , 14 , 15 , 16 ].…”