Synthesis and biological evaluation of 99mTc tricarbonyl complex of O,O′‐diethylethylenediamine‐N,N′‐di‐3‐propanoate as potential tumour diagnostic agent

Abstract

The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O′‐diethylethylenediamine‐N,N′‐di‐3‐propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L') and diacid ligand (L''), with characteristic donor atom array N,N,O. Ligand L was successfully labelled with 99mTc at pH = 9 by coordination with the octahedral fac‐[99mTc(CO)3(H2O)3]+ intermediate, forming the main radioproduct fac‐[99mTcL′(CO)3] (Tc1). The 99mTc complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 ± 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 ± 1.19%ID g−1 in the liver, 5.87 ± 0.54%ID g−1 in the lungs and 3.17 ± 0.33%ID g−1 in the ovary at 30 min post‐injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright © 2015 John Wiley & Sons, Ltd.