Development and characterization of a ^99mTc-tricarbonyl-labelled estradiol derivative obtained by 'Click Chemistry' with potential application in estrogen receptors imaging.

Tejería, María Emilia; Giglio, Javier; Dematteis, Silvia; Rey, Ana

Assessment of the presence of estrogen receptors in breast cancer is crucial for treatment planning. With the objective to develop a potential agent for estrogen receptors imaging, we present the development and characterization of a 99mTc-tricarbonyl-labelled estradiol derivative. Using ethinylestradiol as starting material, an estradiol derivative bearing a 1,4-disubstituted 1,2,3-triazole-containing tridentate ligand system was synthesized by 'Click Chemistry' and fully characterized. Labelling with high yield and radiochemical purity was achieved through the formation of a 99mTc-tricarbonyl complex. The radiolabelled compound was stable, exhibited moderate binding to plasma protein (approximately 33%) and lipophilicity in the adequate range (logP 1.3 ± 0.1 at pH 7.4). Studies in MCF7 showed promising uptake values (approximately 2%). However, more than 50% of the activity is quickly released from the cell. Biodistribution experiments in normal rats confirmed the expected 'in vivo' stability of the radiotracer but showed very high gastrointestinal and liver activity, which is inconvenient for in vivo applications. Taking into consideration the well-documented influence of the chelating system in the physicochemical and biological behaviour of technetium-labelled small biomolecules, research will be continued using the same pharmacophore but different complexation modalities of technetium.

BREAST cancer treatment; BREAST cancer diagnosis; ESTROGEN receptors; TECHNETIUM; RADIOCHEMICAL purification; THERAPEUTICS

Journal of Labelled Compounds & Radiopharmaceuticals, 2017, Vol 60, Issue 11, p521

0362-4803

Academic Journal

10.1002/jlcr.3527