سنتز لیگاند متوکسی آمیدو زانتات و بهینه‌سازی شرایط نشان‌دارسازی با mTc99 به عنوان عامل تصویربرداری SPECT

عرب حلوایی باقری, زهرا; آقامیری, سیدمحمودرضا; ستارزاده خامنه, الهام; کاکائی, سعید; یوسف نیا, حسن

doi:10.24200/nst.2022.1039.1701

نوع مقاله : مقاله پژوهشی

نویسندگان

¹ گروه مهندسی پرتو پزشکی، دانشگاه شهید بهشتی، صندوق پستی: 4716-19839، تهران- ایران

² پژوهشکده کاربرد پرتوها، پژوهشگاه علوم و فنون هسته‌ای، صندوق پستی: 3486-11365، تهران ـ ایران

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

چکیده

هدف از پژوهش حاضر، سنتز، ترکیب متوکسی آمیدو زانتات MAX و نشان‌دارسازی آن با رادیونوکلیید ^mTc⁹⁹ به عنوان یک عامل تشخیصی نوین جهت تصویربرداری توموگرافی رایانه‌ای تک فوتونی (SPECT) می‌باشد. لیگاند فوق از واکنش بین دو ماده‌ی کلرواستامید (Chloroacetamide) و مشتقات زانتات (Xanthate) با نسبت‌های مولی معین سنتز شد. سپس فرایند نشان‌دارسازی لیگاند MAX از طریق دوشیدن ^mTc⁹⁹ از ژنراتور (^mTc⁹⁹Mo/⁹⁹) و به روش مستقیم انجام گرفت. به این ترتیب که قلع کلرید به عنوان عامل کاهنده مورد استفاده قرار گرفت و اثر پارامترهایی از قبیل عوامل افزودنی از جمله اسید آسکوربیک، تغییر غلظت عامل شلات‌کننده و pH جهت بهینه‌سازی شرایط نشان‌دارسازی مورد ارزیابی قرار گرفت. شناسایی و تشخیص محصولات شیمیایی به وسیله‌ی طیف‌سنجی‌های مادون قرمز (FTIR) و رزونانس مغناطیسی هسته (NMR) انجام گرفت. میزان نشان‌دارسازی کمپلکس در دمای آزمایشگاه %93 برآورد شد. رادیوداروی نوین ^mTc-MAX⁹⁹ با خلوص رادیونوکلییدی و رادیوشیمیایی بالاتر از %90 می‌تواند به عنوان یک عامل تشخیصی نوید بخش در مطالعات کلینیکی و پیش‌بالینی مورد استفاده قرار گیرد که در مطالعات آینده به آن پرداخته خواهد شد.

کلیدواژه‌ها

عنوان مقاله [English]

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

نویسندگان [English]

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

چکیده [English]

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.

کلیدواژه‌ها [English]

Labeling
Chelator
Methoxy amido xanthate (MAX)
SPECT
Technetium-99m

مراجع

1. 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).

2. 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).

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

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

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

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

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

8. 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).

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

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

11. 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).

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

13. 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).

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

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

16. 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).

17. 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).

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

مجله علوم و فنون هسته ای

سنتز لیگاند متوکسی آمیدو زانتات و بهینه‌سازی شرایط نشان‌دارسازی با mTc99 به عنوان عامل تصویربرداری SPECT

مراجع

مراجع

1. 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).

2. 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).

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

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

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

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

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

8. 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).

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

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

11. 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).

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

13. 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).

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

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

16. 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).

17. 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).

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

دوره 44، شماره 2 - شماره پیاپی 104
تیر 1402
صفحه 13-21

سنتز لیگاند متوکسی آمیدو زانتات و بهینه‌سازی شرایط نشان‌دارسازی با mTc99 به عنوان عامل تصویربرداری SPECT

مراجع

مراجع

1. 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).

2. 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).

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

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

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

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

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

8. 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).

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

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

11. 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).

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

13. 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).

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

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

16. 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).

17. 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).

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

دوره 44، شماره 2 - شماره پیاپی 104تیر 1402صفحه 13-21

دوره 44، شماره 2 - شماره پیاپی 104
تیر 1402
صفحه 13-21