A novel 99m Tc-diester complex as tumor targeting agent: Synthesis, radiolabeling, and biological distribution study

• Published in: Journal of labelled compounds & radiopharmaceuticals 2020-06, Vol.63 (8), p.376-385
• Main Authors: Shamsel-Din, Hesham A, Gizawy, Mohamed A, Zaki, Elsayed G, Elgendy, Amr
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Chemistry Techniques, Synthetic; Esters - chemical synthesis; Esters - chemistry; Female; Humans; Isotope Labeling; MCF-7 Cells; Mice; Organotechnetium Compounds - chemical synthesis; Organotechnetium Compounds - chemistry; Organotechnetium Compounds - pharmacokinetics; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Technetium - chemistry; Tissue Distribution
• ISSN: 0362-4803; 1099-1344; 1099-1344
• DOI: 10.1002/jlcr.3841

The target of this study is the synthesis of a new diester derivative and radiolabeling with one of the most effective diagnostic radioisotopes to be investigated as a novel targeting radiotracer for tumor imaging. 10-[2-(9-Carboxynonanoyloxy)propoxy]-10-oxodecanoic acid was synthesized in excellent yield and characterized by Fourier-transform infrared spectroscopy, mass, H-NMR, and C-NMR spectra. The diester was technetium-99m ( Tc) radiolabeled by direct technique using sodium dithionite as a reducing agent. The labeling parameters such as diester amount, reducing agent amount, pH of the medium, and reaction time were optimized. High radiochemical yield of 95.10 ± 0.41% and in vitro stability in serum up to 12 h have been obtained on complexation of the synthesized diester with Tc-99m. Evaluation of the diester anticancer activity against breast cancer cell line (MCF-7) showed high percent of inhibition about 61.5% at 100 μg/ml. The rhenium complex of the diester was synthesized and characterized by liquid chromatography-mass spectrometry (ESI) and elemental analysis depending on the strong chemical resemblance between Tc and Re. Biodistribution studies of Tc-diester complex showed high target to nontarget ratio (T/NT) equals 6.24 ± 0.09 in tumor-bearing mice at 30-min postinjection, suggesting this complex could be used as hopeful solid tumor-imaging agent.