Target-specific Tc(CO)3-complexes for in vivo imaging

•99mTc/Re-tricarbonyl complexes stabilized by pyrazolyl-based chelators are reviewed.•The biological properties of various target-specific 99mTc-complexes are discussed.•The targeting properties of 99mTc-labeled tumor-seeking peptides are presented.•99mTc-labeled nanoparticles allowed the visualization of SLN at the preclinical level.

In recent years, the remarkable characteristics of the organometallic precursor fac-[M(CO)3(H2O)3]+ (M = Re, Tc) introduced by Alberto and co-workers brought renewed interest to the development of low-oxidation 99mTc-based radioactive probes. Considering our interest in the design of target-specific radioactive probes for SPECT-imaging and targeted systemic radiotherapy, we have been involved in the study of the chemistry of fac-[M(CO)3]+ (M = Re, Tc) with chelators combining a pyrazolyl unit with aliphatic amines and/or carboxylic acids or thioethers. This review describes our research efforts in the field, giving particular emphasis to the biological properties of Re(I) and 99mTc(I) complexes anchored by those type of chelators. We aim to highlight the versatility of the pyrazolyl-containing chelators, which allowed the successful labeling of a wide range of relevant biomolecules, spanning from small lipophilic organic molecules, such as quinazoline derivatives or DNA-binders, to tumor-seeking peptides for in vivo receptor targeting. Noteworthy is also the possibility of labeling polymeric nanoparticles based on dextran for sentinel lymph node detection (SLND), which has been one of our most successful achievements in recent years. These radiolabeled nanoparticles allowed the visualization of the SLN accurately at the preclinical level.

Graphical abstractThis review describes our research efforts toward the design of target-specific radioactive probes for SPECT-imaging and targeted systemic radiotherapy, giving particular emphasis to the biological properties of Re(I) and 99mTc(I) complexes anchored by chelators combining a pyrazolyl unit with aliphatic amines and/or carboxylic acids or thioethers, and a targeting biomolecule.Figure optionsDownload full-size imageDownload as PowerPoint slide