Theoretical study of Re and Tc DMSA complexes

The aim of this study is to develop a new strategy for developing multimeric molecule probes used for SPECT imaging. Thus, multimeric concept has been used to synthesise FR-targeting imaging probes (monomeric, dimeric and tetrameric folate derivatives). The novel folate derivatives were radiolabelled with Tc using tricine and trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS) as coligands, and resulted in three Tc-complexes (Tc-HYNIC-D0-PEGFA1, Tc-HYNIC-D1-PEG-FA2, Tc-HYNIC-D2-PEG-FA4). To investigate their affinity properties, cell uptake, biodistribution and micro-SPECT/CT imaging were evaluated, respectively. The folate derivatives had hydrophilic properties. The biodistribution results of radiotracers in KB tumor-bearing mice displayed considerable kidney and tumour uptakes at all time-points. In cell uptake study, all the radioligands demonstrated increased tracer uptakes with time. As expected, the micro-SPECT/CT imaging showed that these radiotracers had high uptakes in KB tumors. Among these radiotracers, TcHYNIC-D0-PEG-FA1 showed very promising biological properties over dimer or tetramer radiofolates. Its maximal tumor accumulation was found at 2 h p.i. (16.30 ± 2.01% ID/g) and almost completely retained over the time of investigation (14.90 ± 0.45% ID/g at 4 h p.i.). The binding affinity of multifolate radiotracers will be studied in the future and the development of multimeric concept of Tc-labelled folate is worth for further evaluation. (NSFC (21271030) and 973 Program of China (2014CB744503)).