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

Abstract

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.