Synthesis of methoxy amido xanthate ligand and optimization of 99mTc labeling conditions as SPECT imaging agent

Arab Halvaiee Bagheri, Z.; Aghamiri, S.M.R.; Sattarzadeh Khameneh, E.; Kakaei, S.; Yousefnia, H.

doi:10.24200/nst.2022.1039.1701

Synthesis of methoxy amido xanthate ligand and optimization of 99mTc labeling conditions as SPECT imaging agent

Document Type : Research Paper

Authors

Z. Arab Halvaiee Bagheri ¹

S.M.R. Aghamiri ¹

E. Sattarzadeh Khameneh ²

S. Kakaei ²

H. Yousefnia ²

¹ Radiation Application Department, Shahid Beheshti University, P.O. Box: 19839-4716, Tehran –Iran

² Radiation Application Research School, Nuclear Science and Technology Research Institute, P. O. Box 11365-3486, Tehran - Iran

https://doi.org/10.24200/nst.2022.1039.1701

Abstract

In the present study, the aim is to synthesize and introduce the combination of methoxy amido xanthate MAX and then label it with 99mTc radionuclide as a novel diagnostic agent for single-photon computed tomography (SPECT) imaging. A chelator-designed ligand was synthesized from a blend of chloroacetamide and xanthate in certain proportions. After that MAX ligand labeling process was performed by directly milking ^99mTc from the generator (⁹⁹Mo / ^99mTc). Thus, tin chloride was employed as a reducing agent, and the effect of parameters such as additives like ascorbic acid, changing the concentration of the cheating agent, and pH were evaluated to optimize the labeling conditions. The product was then identified by infrared spectroscopy (FTIR) and magnetic resonance imaging (NMR). Labeling of the complex at laboratory temperature was determined to be 93%. The new ^99mTc-MAX radiopharmaceutical with a radionuclide and radiochemical purity of over 90% can be used as an encouraging diagnostic agent in clinics and preclinical studies, which will be addressed in future studies.

Highlights

S.M. Ghoreishi, et al., Technetium-99m chelator-free radiolabeling of specific glutamine tumor imaging nanoprobe: in vitro and in vivo evaluations, Int. J. Nanomedicine, 13, 4613 (2018).

A. Boschi, L. Uccelli, P. Martini, A picture of modern Tc-99m radiopharmaceuticals: Production, chemistry, and applications in molecular imaging, Appl. Sci., 9, 2526 (2019).

D. Sarko, et al, Bifunctional chelators in the design and application of radiopharmaceuticals for oncological diseases, Current Medicinal Chemistry, 19, 2667-2688 (2012).

C.F. Ramogida, C. Orvig, Tumour targeting with radiometals for diagnosis and therapy, Chemical Communications, 49, 4720-4739 (2013).

M.U. Akbar, et al, A review on evaluation of technetium-99m labeled radiopharmaceuticals, Journal of Radioanalytical and Nuclear Chemistry, 310, 477-493 (2016).

S.J. Flora, V. Pachauri, Chelation in metal intoxication, International Journal of Environmental Research and Public Health, 7, 2745-2788 (2010).

F.A. Carey, R.J. Sundberg, Part B: Reactions and Synthesis, (Springer, 2013).

Z. Pourmanouchehri, et al, Magnetic Nanocarrier Containing 68 Ga–DTPA Complex for Targeted Delivery of Doxorubicin, Journal of Inorganic and Organometallic Polymers and Materials, 28, 1980-1990 (2018).

S. Kakaei, et al, Targeted Drug Delivery of Teniposide by Magnetic Nanocarrier, Current Nanoscience, 16, 608-616 (2020).

E. Sattarzadeh, et al, 68 Ga-radiolabeled magnetic nanoparticles for PET–MRI imaging, Journal of Radioanalytical and Nuclear Chemistry, 317, 1333-1339 (2018).

H. Tayeri, et al, Optimized production, quality control and biological assessment of 68-Ga-bleomycin as a possible PET imaging agent, International Journal of Radiation Research, 18, 237-241 (2020).

E.S. Khameneh, et al, Preparation of dual-modality yttrium-90 radiolabeled nanoparticles for therapeutic investigation, Radiochimica Acta, 106, 897-907 (2018).

M. Korany, et al, Synthesis and radiolabeling of vitamin C-stabilized selenium nanoparticles as a promising approach in diagnosis of solid tumors, Journal of Radioanalytical and Nuclear Chemistry, 325, 237-244 (2020).

L. Little, G. Poling, J. Leja, Infrared spectra of xanthate compounds: II. Assignment of vibrational frequencies, Canadian Journal of Chemistry, 39, 745-754 (1961).

M. Motaleb, et al, Synthesis, radioiodination and biological evaluation of a novel phthalimide derivative, Journal of Radioanalytical and Nuclear Chemistry, 307, 363-372 (2016).

H.A. Shamsel‐Din, A novel 99mTc‐diester complex as tumor targeting agent: synthesis, radiolabeling, and biological distribution study, Journal of Labelled Compounds and Radiopharmaceuticals, 63, 376-385, (2020).

E. Gharepapagh, et al, Preparation, biodistribution and dosimetry study of Tc-99m labeled N-doped graphene quantum dot nanoparticles as a multimodular radiolabeling agent, New Journal of Chemistry, 45, 3909-3919, (2021).

A.B. Hughes, Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4-Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis. (Wiley-VCH, 2011).

Keywords

Labeling

Chelator

Methoxy amido xanthate (MAX)

SPECT

Technetium-99m

20.1001.1.17351871.1402.44.2.2.4

S.M. Ghoreishi, et al., Technetium-99m chelator-free radiolabeling of specific glutamine tumor imaging nanoprobe: in vitro and in vivo evaluations, Int. J. Nanomedicine, 13, 4613 (2018).

A. Boschi, L. Uccelli, P. Martini, A picture of modern Tc-99m radiopharmaceuticals: Production, chemistry, and applications in molecular imaging, Appl. Sci., 9, 2526 (2019).

D. Sarko, et al, Bifunctional chelators in the design and application of radiopharmaceuticals for oncological diseases, Current Medicinal Chemistry, 19, 2667-2688 (2012).

C.F. Ramogida, C. Orvig, Tumour targeting with radiometals for diagnosis and therapy, Chemical Communications, 49, 4720-4739 (2013).

M.U. Akbar, et al, A review on evaluation of technetium-99m labeled radiopharmaceuticals, Journal of Radioanalytical and Nuclear Chemistry, 310, 477-493 (2016).

S.J. Flora, V. Pachauri, Chelation in metal intoxication, International Journal of Environmental Research and Public Health, 7, 2745-2788 (2010).

F.A. Carey, R.J. Sundberg, Part B: Reactions and Synthesis, (Springer, 2013).

Z. Pourmanouchehri, et al, Magnetic Nanocarrier Containing 68 Ga–DTPA Complex for Targeted Delivery of Doxorubicin, Journal of Inorganic and Organometallic Polymers and Materials, 28, 1980-1990 (2018).

S. Kakaei, et al, Targeted Drug Delivery of Teniposide by Magnetic Nanocarrier, Current Nanoscience, 16, 608-616 (2020).

E. Sattarzadeh, et al, 68 Ga-radiolabeled magnetic nanoparticles for PET–MRI imaging, Journal of Radioanalytical and Nuclear Chemistry, 317, 1333-1339 (2018).

H. Tayeri, et al, Optimized production, quality control and biological assessment of 68-Ga-bleomycin as a possible PET imaging agent, International Journal of Radiation Research, 18, 237-241 (2020).

E.S. Khameneh, et al, Preparation of dual-modality yttrium-90 radiolabeled nanoparticles for therapeutic investigation, Radiochimica Acta, 106, 897-907 (2018).

M. Korany, et al, Synthesis and radiolabeling of vitamin C-stabilized selenium nanoparticles as a promising approach in diagnosis of solid tumors, Journal of Radioanalytical and Nuclear Chemistry, 325, 237-244 (2020).

L. Little, G. Poling, J. Leja, Infrared spectra of xanthate compounds: II. Assignment of vibrational frequencies, Canadian Journal of Chemistry, 39, 745-754 (1961).

M. Motaleb, et al, Synthesis, radioiodination and biological evaluation of a novel phthalimide derivative, Journal of Radioanalytical and Nuclear Chemistry, 307, 363-372 (2016).

H.A. Shamsel‐Din, A novel 99mTc‐diester complex as tumor targeting agent: synthesis, radiolabeling, and biological distribution study, Journal of Labelled Compounds and Radiopharmaceuticals, 63, 376-385, (2020).

E. Gharepapagh, et al, Preparation, biodistribution and dosimetry study of Tc-99m labeled N-doped graphene quantum dot nanoparticles as a multimodular radiolabeling agent, New Journal of Chemistry, 45, 3909-3919, (2021).

A.B. Hughes, Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4-Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis. (Wiley-VCH, 2011).