Estrogen receptor targeting with genistein radiolabeled Technetium-99m as radiotracer of breast cancer: Its optimization, characterization, and predicting stability constants by DFT calculation

Danni Ramdhani; Nita Listiani; Maula Eka Sriyani; Eva Maria W; Hiroshi Watabe; Resmi Mustarichie; Sri Agung Fitri Kusuma; Regaputra S Janitra

doi:10.1016/j.heliyon.2023.e13169

Estrogen receptor targeting with genistein radiolabeled Technetium-99^m as radiotracer of breast cancer: Its optimization, characterization, and predicting stability constants by DFT calculation

Heliyon. 2023 Jan 21;9(2):e13169. doi: 10.1016/j.heliyon.2023.e13169. eCollection 2023 Feb.

Authors

Danni Ramdhani^{1

2}, Nita Listiani¹, Maula Eka Sriyani³, Eva Maria W³, Hiroshi Watabe², Resmi Mustarichie¹, Sri Agung Fitri Kusuma⁴, Regaputra S Janitra⁵

Affiliations

¹ Department of Pharmaceutical Analysis and Medicinal Chemistry, Padjadjaran University, Sumedang, West Java, 45363, Indonesia.
² Division of Radiation Protection and Safety Control, Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai 980-0845, Japan.
³ Applied Nuclear Science and Technology Center (PSTNT), National Nuclear Energy Agency of Indonesia (BATAN), Bandung, West Java 40116, Indonesia.
⁴ Department of Biology Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia.
⁵ Biotechnology Master Program, Faculty of Postgraduate, Padjadjaran University, Bandung 40132, Indonesia.

Abstract

Objective: Genistein is an isoflavone molecule with a high affinity for estrogen receptors (ER), which could lead to the mechanism of selective estrogen receptor modulators (SERMs) in breast cancer. Genistein labeling with technetium-99^m can be a new promising strategy for diagnostic breast cancer. In this research, we evaluate the physicochemical characteristics of the [^99mTc]Tc-genistein complex and describe the optimal labeling method parameters. We also calculated density functional theory to study the stability constants to support complex formation analysis (DFT).

Methods: The genistein was directly labeled with ^99mTc, and its stability as well as its potential for usage as a radiotracer were all investigated. DFT calculations with thermodynamic cycles to determine chemical coordination models and calculate thermodynamic constants of complex more accurately.

Results: The radiochemical purity of [^99mTc]Tc-genistein showed a high yield of 93.25% ± 0.30% and had good physicochemical properties. The stability of the Tc(IV)-genistein complex was confirmed by DFT calculations at a value of 99.0822.

Conclusions: As a result, [^99mTc]Tc-genistein could be a potential radiotracer kit for SPECT imaging of breast cancer.

Keywords: Breast cancer; Density functional theory; Estrogen receptors β; Genistein; Physicochemical properties; Technetium-99 m; Thermodynamic stability.