Applications of "Hot" and "Cold" Bis(thiosemicarbazonato) Metal Complexes in Multimodal Imaging. Issue 3 (6th May 2016)

• Record Type: Journal Article
• Authors: Cortezon‐Tamarit, Fernando; Sarpaki, Sophia; Calatayud, David G.; Mirabello, Vincenzo; Pascu, Sofia I.
• Is Part Of: Chemical record. Volume 16:Issue 3(2016)
• Page Start: 1380
• Page End: 1397
• Publication Date: 2016-05-06
• Subjects: cancer -- hypoxia -- imaging agents -- metal complexes; Chemistry -- Periodicals; 540
• DOI: 10.1002/tcr.201500292
• Languages: English
• ISSNs: 1527-8999

Abstract

Abstract: The applications of coordination chemistry to molecular imaging has become a matter of intense research over the past 10 years. In particular, the applications of bis(thiosemicarbazonato) metal complexes in molecular imaging have mainly been focused on compounds with aliphatic backbones due to the in vivo imaging success of hypoxic tumors with PET (positron emission tomography) using 64 CuATSM [copper (diacetyl‐bis(N4‐methylthiosemicarbazone))]. This compound entered clinical trials in the US and the UK during the first decade of the 21 st century for imaging hypoxia in head and neck tumors. The replacement of the ligand backbone to aromatic groups, coupled with the exocyclic N's functionalization during the synthesis of bis(thiosemicarbazones) opens the possibility to use the corresponding metal complexes as multimodal imaging agents of use, both in vitro for optical detection, and in vivo when radiolabeled with several different metallic species. The greater kinetic stability of acenaphthenequinone bis(thiosemicarbazonato) metal complexes, with respect to that of the corresponding aliphatic ATSM complexes, allows the stabilization of a number of imaging probes, with special interest in "cold" and "hot" Cu(II) and Ga(III) derivatives for PET applications and 111 In(III) derivatives for SPECT (single‐photon emission computed tomography) applications, whilst Zn(II) derivatives display optical imaging properties in cells, with enhanced fluorescence emission and lifetime with respect to the free ligands. Preliminary studies have shown that gallium‐based acenaphthenequinone bis(thiosemicarbazonato) complexes are also hypoxia selective in vitro, thus increasing the interest in them as new generation imaging agents for in vitro and in vivo applications. Abstract : This review provides a personal account of the general background on the use of bis(thiosemicarbazonato) metal complexes in molecular imaging, which is central to recent work in this field. We have a long‐lasting interest in understanding the structure‐function relationships underlining the potential of bis(thiosemicarbazonato) metal complexes for applications in multimodal imaging involving PET/SPECT/optical imaging modalities. The molecular design and the selectivity of this class of compounds for the evaluation of hypoxia is also discussed.