Radionuclide tagging of biomolecules

Authors

DOI:

https://doi.org/10.35954/SM2024.43.2.4.e402

Keywords:

Technetium/ administration & dosage., lutecio/administration & dosage, isotope labeling, chelating agents, radiation, radioisotopes, technetium/ administration & dosage

Abstract

Introduction: The labeling of biomolecules with radionuclides is a fundamental technique in nuclear medicine that allows the visualization and treatment of various diseases, especially cancer.

Materials and methods: This work discusses in detail the methods and applications of this technology, including radionuclide selection, conjugation to biomolecules using chelating agents such as dodecane tetraacetic acid (DOTA), Diethylene Triamino Penta Acetic Acid (DTPA), Hydrazinonicotinic acid (HYNIC), and purification and characterization processes.

Results: Specific examples are presented, such as the labeling of Bevacizumab and Tocilizumab with 99mTc and 177Lu, highlighting their applications in cancer imaging and therapy. In addition, clinical applications and future research in the field are explored, emphasizing the potential for personalized medicine and combination therapies.

Discussion: Radionuclide tagging technology continues to advance, promising significant improvements in the diagnosis and treatment of complex diseases, offering accurate and efficient tools for healthcare management. This chapter provides a comprehensive overview of the techniques, case studies and the impact of this methodology in clinical practice.

This article was approved by the Editorial Board.

Received for review: March 2024.
Accepted for publication: June 2024.
Correspondence: Nuclear Research Center. Mataojo 2055. CP. 11400, Montevideo, Uruguay. Tel: 598(2)99472572.
Contact e-mail: pcabral@cin.edu.uy

 

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Author Biographies

Pablo Cabral, Universidad de la República de Uruguay

Facultad de Ciencias, Departamento de Radiofarmacia, Centro de Investigaciones Nucleares. Montevideo, Uruguay. 

Contributions to the manuscript: Conception; design; data analysis; interpretation and discussion of results and approval of the final version.

Ximena Aida Camacho Damata, Universidad de la República de Uruguay

Facultad de Ciencias, Departamento de Radiofarmacia, Centro de Investigaciones Nucleares. Montevideo, Uruguay. 

Contributions to the manuscript: Design, data acquisition, writing, critical revision, interpretation and discussion of results.

References

Dhoundiyal S, Srivastava S, Kumar S, Singh G, Ashique S, Pal R, et al. Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation. Eur J Med Res 2024 Jan 5; 29(1):26. PMID: 38183131; PMCID: PMC10768149. https://doi.org/10.1186/s40001-023-01627-0

Parakh S, Lee ST, Gan HK, Scott AM. Radiolabeled Antibodies for Cancer Imaging and Therapy. Cancers (Basel) 2022 Mar 11; 14(6):1454. PMID: 35326605; PMCID: PMC8946248. https://doi.org/10.3390/cancers14061454

Fu R, Carroll L, Yahioglu G, Aboagye EO, Miller PW. Antibody Fragment and Affibody ImmunoPET Imaging Agents: Radiolabelling Strategies and Applications. Chem Med Chem 2018 Dec 6; 13(23):2466-2478. Epub 2018 Nov 15. PMID: 30246488; PMCID: PMC6587488. https://doi.org/10.1002/cmdc.201800624

Witney TH, Blower PJ. The chemical tool-kit for molecular imaging with radionuclides in the age of targeted and immune therapy. Cancer Imaging 2021 Jan 30; 21(1):18. PMID: 33516256; PMCID: PMC7847158. https://doi.org/10.1186/s40644-021-00385-8

Lepareur N, Ramée B, Mougin-Degraef M, Bourgeois M. Clinical Advances and Perspectives in Targeted Radionuclide Therapy. Pharmaceutics 2023 Jun 14; 15(6):1733. PMID: 37376181; PMCID: PMC10303056. https://doi.org/10.3390/pharmaceutics15061733

Talip Z, Favaretto C, Geistlich S, Meulen NPV. A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb. Molecules 2020 Feb 20; 25(4):966. PMID: 32093425; PMCID: PMC7070971. https://doi.org/10.3390/molecules25040966

Srivastava SC. Criteria for the selection of radionuclides for targeting nuclear antigens for cancer radioimmunotherapy. Cancer Biother Radiopharm 1996 Feb; 11(1):43-50. PMID: 10851519. https://doi.org/10.1089/cbr.1996.11.43

Rathmann SM, Ahmad Z, Slikboer S, Bilton HA, Snider DP, Valliant JF. The Radiopharmaceutical Chemistry of Technetium-99m. In: Lewis J, Windhorst A, Zeglis B. (eds). Radiopharmaceutical Chemistry. Springer, Cham, 2019. p. 311-333. https://doi.org/10.1007/978-3-319-98947-1_18

Duatti A. Fundamentals of Technetium-99mRadiopharmaceutical Chemistry. In: Khalil, M.M. (eds). Basic Sciences of Nuclear Medicine. p. 73-101. Springer, Cham, 2021. Available from: https://doi.org/10.1007/978-3-030-65245-6_4

Sharma S, Pandey MK. Radiometals in Imaging and Therapy: Highlighting Two Decades of Research Pharmaceuticals 2023; 16(10):1460. https://doi.org/10.3390/ph16101460

George SC, Samuel EJJ. Developments in 177Lu-based radiopharmaceutical therapy and dosimetry. Front Chem 2023 Jul 31; 11:1218670. https://doi.org/10.3389/fchem.2023.1218670 Erratum in: Front Chem. 2024 Apr 17; 12:1410803. PMID: 37583569; PMCID: PMC10424930. https://doi.org/10.3389/fchem.2024.1410803

Das T, Banerjee S. Theranostic Applications of Lutetium-177 in Radionuclide Therapy. Curr Radiopharm. 2016; 9(1):94-101. PMID: 25771364. https://doi.org/10.2174/1874471008666150313114644

De la Vieja A, Riesco-Eizaguirre G. Radio-Iodide Treatment: From Molecular Aspects to the Clinical View. Cancers (Basel) 2021 Feb 27; 13(5):995. PMID: 33673669; PMCID: PMC7957486. https://doi.org/10.3390/cancers13050995

Palot Manzil FF, Kaur H. Radioactive Iodine for Thyroid Malignancies. 2023 Nov 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024 Jan–. PMID: 35593874.

Liu S. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Adv Drug Deliv Rev 2008 Sep; 60(12):1347-70. Epub 2008 Apr 23. PMID: 18538888; PMCID: PMC2539110. https://doi.org/10.1016/j.addr.2008.04.006

Edelmann MR. Radiolabelling small and biomolecules for tracking and monitoring. RSC Adv 2022 Nov 11; 12(50):32383-32400. PMID: 36425706; PMCID: PMC9650631. https://doi.org/10.1039/d2ra06236d

Cooper MS, Sabbah E, Mather SJ. Conjugation of chelating agents to proteins and radiolabeling with trivalent metallic isotopes. Nat Protoc 2006; 1(1):314-7. PMID: 17406251. https://doi.org/10.1038/nprot.2006.49

Dijkgraaf I, Agten S, Bauwens M, Hackeng T. Strategies for Site-Specific Radiolabeling of Peptides and Proteins [Internet].Radiopharmaceuticals - Current Research for Better Diagnosis and Therapy. IntechOpen; 2022. https://doi.org/10.5772/intechopen.99422

Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997; 57(20):4593-99.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastic colorectal cancer. N Engl J Med 2004; 350:2335-42.

Camacho X, García MF, Calzada V, Fernández M, Moreno M, De Aguiar R, et al. [99mTc(CO)3]-radiolableled Bevacizumab: in vitro and in vivo evaluation in melanoma model. Oncology 2013; 82:200-209.

Camacho X, García MF, Calzada V, Fernández M, Porcal W, Alonso O, et al. Synthesis and evaluation of (99m)Tc chelateconjugated bevacizumab. Curr Radiopharm 2013 Mar; 6(1):12-9. PMID: 23035645. https://doi.org/10.2174/1874471011306010003

Camacho X, García MF, Calzada V, Fernández M, Alonso O, Gambini JP, et al. 99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma. J Anal Oncol 2014; 3(1):53-64.

Camacho X, Calzada V, Fernandez M, Alonso O, Chammas R, Riva E, et al. 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma. Curr Radiopharm 2017; 10(1):21-28. https://doi.org/10.2174/1874471009666161010155246

Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother. 2017 Sep 2; 13(9):1972-1988. https://doi.org/10.1080/21645515.2017.1316909

Avci A, Feist E, Burmester G. Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What's the Difference? BioDrugs. 2018 Dec; 32(6):531-546. https://doi.org/10.1007/s40259-018-0320-3

Okuda Y. Review of tocilizumab in the treatment of rheumatoid arthritis. Biologics 2008 Mar; 2(1):75-82. https://doi.org/10.2147/btt.s1828

Gutiérrez E, Camacho X, Calzada V, Fernández M, García MF, Porcal W, et al. 99mTc-Tocilizumab un nuevo agente de imagen molecular en Mieloma Múltiple. Salud Mil [Internet]. 31 de diciembre de 2012 [citado 11 de octubre de 2023]; 31(1):10-2. https://doi.org/10.35954/SM2012.31.1.2

Camacho X, Machado CL, García MF, Fernández M, Oddone N, Benech J, et al. Tocilizumab Labeling with 99mTechnetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma. Anticancer Agents Med Chem 2017; 17(9):1267-1277. https://doi.org/10.2174/1871520617666170213144917

Kumar K. Radiolabeled Compounds forDiagnosis and Treatment of Cancer. Molecules 2021 Oct 15; 26(20):6227. https://doi.org/10.3390/molecules26206227

Kręcisz P, Czarnecka K, Królicki L, Mikiciuk-Olasik E, Szymański P. Radiolabeled Peptides and Antibodies in Medicine. Bioconjug Chem 2021 Jan 20; 32(1):25-42. Epub 2020 Dec 16. PMID: 33325685; PMCID: PMC7872318. https://doi.org/10.1021/acs.bioconjchem.0c00617

Salmanoglu E, Kim S, Thakur ML. Currently Available Radiopharmaceuticals for Imaging Infection and the Holy Grail. Semin Nucl Med 2018 Mar; 48(2):86-99. PMID: 29452623; PMCID: PMC6487501. https://doi.org/10.1053/j.semnuclmed.2017.10.003

MacRitchie N, Frleta-Gilchrist M, Sugiyama A, Lawton T, McInnes IB, Maffia P. Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment. Pharmacol Ther 2020 Jul; 211:107550. Epub 2020 Apr 20. PMID: 32325067. https://doi.org/10.1016/j.pharmthera.2020.107550

Camacho Damata XA, Perroni C, Cabrera M, Tassano M, Longo Machado CM, Carneiro C de G, et al. 99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple. Salud Mil [Internet]. 29 de mayo de 2023 [citado 11 de octubre de 2023]; 42(1):e302. https://doi.org/10.35954/SM2023.42.1.4.e302

Garattini L, Padula A. Precision medicine and monoclonal antibodies: breach of promise? Croat Med J. 2019 Jun 13; 60(3):284-289. PMID: 31187957; PMCID: PMC6563176. https://doi.org/10.3325/cmj.2019.60.284

Di Paolo A, Luci G. Personalized Medicine of Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacogenetics, Therapeutic Drug Monitoring, and Beyond. Front Pharmacol 2021 Feb 8; 11:610806. PMID: 33628180; PMCID: PMC7898166. https://doi.org/10.3389/fphar.2020.610806

Salih S, Alkatheeri A, Alomaim W, Elliyanti A. Radiopharmaceutical Treatments for Cancer Therapy, Radionuclides Characteristics, Applications, and Challenges. Molecules 2022 Aug 16; 27(16):5231. PMID: 36014472; PMCID: PMC9415873. https://doi.org/10.3390/molecules27165231

van der Meulen NP, Strobel K, Lima TVM. New Radionuclides and Technological Advances in SPECT and PET Scanners. Cancers (Basel) 2021 Dec 8; 13(24):6183. PMID: 34944803; PMCID: PMC8699425. https://doi.org/10.3390/cancers13246183

Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 2020; 19:589-608. https://doi.org/10.1038/s41573-020-0073-9

Kerr CP, Grudzinski JJ, Nguyen TP, Hernandez R, Weichert JP, Morris ZS. Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment. Pharmaceutics 2022 Dec 30; 15(1):128. PMID: 36678756; PMCID: PMC9865370. https://doi.org/10.3390/pharmaceutics15010128

Published

2024-09-03

How to Cite

1.
Cabral P, Camacho Damata XA. Radionuclide tagging of biomolecules. Salud mil [Internet]. 2024 Sep. 3 [cited 2026 Jun. 10];43(2):e402. Available from: https://revistasaludmilitar.uy/ojs/index.php/Rsm/article/view/433

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