Study of the accumulation of gallium-68-labeled folic acid conjugates in various etiologies inflammation foci

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Abstract

In recent years, folate receptors have been considered as a target for radiopharmaceutical drugs. For this purpose, new, previously unexplored compounds based on folic acid were synthesized.

Objective. Study of the accumulation of gallium-68-labeled folic acid conjugates in various etiologies inflammation foci.

Material and methods. The objects of the research were folic acid derivatives labeled with gallium-68. Systemic juvenile idiopathic arthritis was chosen as a pathology model. Acute inflammatory processes of soft tissues of septic and aseptic etiology were selected as differential models.

Results. The results obtained in the study showed a significantly elevated level of accumulation in the juvenile idiopathic arthritis focus compared to healthy rat paws and accumulation in the foci of differential models of the inflammatory process, which confirms the macrophage-mediated pathway of accumulation of the studied compounds.

Conclusion. The data obtained allow us to conclude about the diagnostic potential of radiolabeled conjugates based on folic acid in the radionuclide diagnosis of rheumatoid and other diseases characterized by a pronounced macrophage immune response.

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About the authors

K. A. Lunyova

A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia; Moscow State Academy of Veterinary Medicine and Biotechnology – MVA by K.I. Skryabin

Author for correspondence.
Email: christfmbc@gmail.com
ORCID iD: 0000-0002-1256-9873

Research Scientist, Laboratory of Preclinical and Clinical Studies of Radiopharmaceuticals; Post-graduate Student, Department of Chemistry

Russian Federation, Moscow; Moscow

A. A. Larenkov

A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia

Email: anton.larenkov@gmail.com
ORCID iD: 0000-0003-4810-4346

Ph.D. (Chem.), Head of the Laboratory of Technology and Methods of Control of Radiopharmaceuticals

Russian Federation, Moscow

M. G. Rakhimov

A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia

Email: marat.rakhimov89@gmail.com
ORCID iD: 0000-0002-7521-5976

Engineer, Laboratory of Technology and Methods of Control of Radiopharmaceuticals

Russian Federation, Moscow

A. S. Lunev

A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia

Email: mr.alekslunev@gmail.com
ORCID iD: 0000-0002-8392-8343

Ph.D. (Biol.), Senior Research Scientist, Laboratory of Preclinical and Clinical Studies of Radiopharmaceuticals

Russian Federation, Moscow

O. E. Klementyeva

A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia

Email: klementyeva.olga@gmail.com
ORCID iD: 0000-0002-6604-0860

Ph.D. (Biol.), Head of the Laboratory of Preclinical and Clinical Studies of Radiopharmaceuticals

Russian Federation, Moscow

F. I. Vasilevich

Moscow State Academy of Veterinary Medicine and Biotechnology – MVA by K.I. Skryabin

Email: f-vasilevich@inbox.ru
ORCID iD: 0000-0003-0786-5317

Dr.Sc. (Veterinary), Professor, Academician of the Russian Academy of Sciences, Head of the Department of Parasitology and Veterinary and Sanitary Expertise

Russian Federation, Moscow

A. E. Machulkin

Lomonosov Moscow State University

Email: alekseymachulkin@rambler.ru
ORCID iD: 0000-0001-7975-0346

Ph.D. (Chem.), Research Scientist

Russian Federation, Moscow

References

  1. Yang D.J., Kim E.E., Inoue T. Targeted molecular imaging in oncology. Ann Nucl Med. 2006; 20(1):1‒11.
  2. Richter M., Zhang H. Receptor-targeted cancer therapy. DNA Cell Biol. 2005; 24(5): 271‒282.
  3. Larenkov A., Rakhimov M., Lunyova K., et al. Phar-macokinetic Properties of 68Galabelled Folic Acid Conjugates: Improvement Using HEHE Tag. Molecules. 2020; 25: 2712.
  4. Chen C., Ke J., Zhou X.E. et al. Structural basis for molecular recognition of folic acid by folate receptors. Nature. 2013; 500(7463): 486‒489.
  5. Necela B.M., Crozier J.A., Andorfer C.A. et al. Folate Receptor-α (FOLR1) Expression and Function in Triple Negative Tumors. PLoS ONE. 2015; 10(3): e0122209.
  6. Müller C. Folate Based Radiopharmaceuticals for Imaging and Therapy of Cancer and Inflammation. Current Pharmaceutical Design. 2012; 18(8): 1058‒1083.
  7. Siegel B.A., Dehdashti F., Mutch D.G., et al. Evaluation of 111In-DTPA- folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results. J. Nucl. Med. 2003; 44: 700‒707.
  8. Parker N., Turk M.J., Westrick E., et al. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005; 338(2): 284‒293.
  9. Evans C.O., Reddy P., Brat D.J., et al. Differential expression of folate receptor in pituitary adenomas. Cancer Res. 2003; 63(14): 4218‒4224.
  10. Fernandez M., Javaid F., Chudasama V. Advances in targeting the folate receptor in the treatment/imaging of cancers. Chem. Sci. 2018; 9(4): 790‒810.
  11. Патент RU 2 480 241 C2. Лечение и диагностика заболеваний, опосредованных макрофагами. Опубликовано: 27.04.2013, Бюл. № 12 (Patent RU 2 480 241 C2. Lechenie i diagnostika zabolevanij, oposredovannyh makrofagami. Opublikovano: 27.04.2013, Bjul. № 12).
  12. Müller C. Folate-Based Radiotracers for PET Imaging—Update and Perspectives. Molecules. 2013; 18: 5005–5031.
  13. Baranski A.C., Schäfer M., Bauder-Wüst U., et al. Improving the Imaging Contrast of 68Ga-PSMA-11 by Targeted Linker Design: Charged Spacer Moieties Enhance the Pharmacokinetic Properties. Bioconjugate chemistry. 2017; 28(9): 2485‒2492.
  14. Fani M., Tamma M.L., Nicolas G.P. et al. In vivo imaging of folate receptor positive tumor xenografts using novel 68Ga-NODAGA-folate conjugates. Mol. Pharm. 2012; 9: 1136–1145.
  15. Государственный стандарт РФ ГОСТ 33044-2014. Принципы надлежащей лабораторной практики. М.: Стандартинформ. 2019.
  16. Larenkov A., Bruskin A., Kodina G. Preparation of highly purified 68Ga solutions via ion exchange in hydrochloric acid–ethanol mixtures. Journal of Radioanalytical and Nuclear Chemistry. 2015; 305.
  17. Larenkov A., Maruk A. Radiochemical purity of 68Ga-BCA-peptides: Separation of all 68Ga species with a single ITLC strip. World Acad. Sci. Eng. Technol. Int. J. Chem. Mol. Nucl. Mater. Metall. Eng. 2016; 10: 1120–1127.
  18. Maruk A.Y., Larenkov A.A. Determination of ionic 68Ga impurity in radiopharmaceuticals: Major revision of radio-HPLC methods. J. Radioanal. Nucl. Chem. 2020; 323: 189–195.
  19. Патент RU 2 612 843 C1. Способ создания биологической модели системного ювенильного идиопатического артрита в эксперименте. Опубликовано: 13.03.2017. Бюл. № 8 (Patent RU 2 612 843 C1. Sposob sozdanija biologicheskoj modeli sistemnogo juvenil'nogo idiopaticheskogo artrita v jeksperimente. Opublikovano: 13.03.2017. Bjul. № 8).
  20. Лунёв А.С. Экспериментальное обоснование возможности применения 68Ga-цитрата для визуализации воспалительных процессов методом позитронно-эмиссионной томографии: Дисс. ... канд. биол. наук. М. 2016; 162 с.
  21. Мухлынина Е.А., Юшков Б.Г. Реакция соединительной ткани различных органов крыс на острое локальное воспаление. Известия Коми научного центра УрО РАН. 2013; 2(14): 42‒44.

Supplementary files

Supplementary Files
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2. Figure 1. Chemical structure of FA-I and FA-II molecules with their constituent fragments labeled: folic acid (vector fragment); NODAGA chelator for 68Ga coordination; linkers; (HE)2-group to optimize pharmacokinetics

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3. Figure 2. Accumulation in the kidneys (%/g) 60 min after intravenous administration of [68Ga]Ga-FA-I and [68Ga]Ga-FA-II in the kidneys of rats in normal conditions and in inflammatory processes of various etiologies

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4. Figure 3. Accumulation of the investigated radiopharmaceutical compounds in the foci of model pathologies

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5. Figure 4. Mean accumulations of [68Ga]Ga-FA-I and [68Ga]Ga-FA-II in paws with juvenile idiopathic arthritis and in healthy paws of rats (% of administered activity)

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6. Figure 5. Mean accumulations of [68Ga]Ga-FA-I and [68Ga]Ga-FA-II in CB and AV foci and in healthy rat muscle tissue (%/g of tissue)

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