RADIATION & RISK
Bulletin of the National Radiation and Epidemiological Registry
since 1992
About the Journal : 2018 : vol. 27, No. 2 : The in vivo evaluation of biodistribution of methionine labeled with gallium-68, potential positron emission tomography agent

The in vivo evaluation of biodistribution of methionine labeled with gallium-68, potential positron emission tomography agent

«Radiation and Risk», 2018, vol. 27, no. 2, pp.97-106

DOI: 10.21870/0131-3878-2018-27-2-97-106

Authors

Tishchenko V.K. – Sen. Res., C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.
Petriev V.M. – Lead. Res., D. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia. Contacts: 4 Korolyov str., Obninsk, Kaluga region, Russia, 249036. Tel.: (484) 399-71-00; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Mikhailovskaya A.A. – Sen. Res., C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.
Smoryzanova O.A. – Sen. Res., C. Sc., Biol. A. Tsyb MRRC, Obninsk, Russia.

Abstract

Positron emission tomography (PET) is one of the most reliable and highly sensitive method for tumor imaging. Over the past decades, PET with radiolabeled amino acids as radiotracers has become a widely used diagnostic tool. Gallium-68 (68Ga) is a promising radionuclide for PET due to its appropriate decay properties and the availability from the 68Ge/68Ga-generator system. For these reasons, we initiated the development of a new agent based on 68Ga-labeled amino acid methionine for cancer imaging. The aim of this study was the evaluation of biodistribution of 68Ga-methionine after intravenous administration in Wistar rats with cholangioma RS-1 xenografts and compare it with 68GaCl3. The samples of organs and tissues were taken at different time intervals after injection and counted in automatic gamma counter. The performed studies were shown that uptake of 68Ga-methionine in tumors increased from 0,28% of injected dose per gram (ID/g) at 5 min to 0,37% ID/g at 1 h, 0,77% ID/g at 3 h, and 0,85% ID/g at 5 h. At the same time the uptake of 68GaCl3 didn’t exceed 0,34% ID/g. High amount of radioactivity (1,56-3,98% ID/g) were observed in blood. Among the soft tissue organs, only liver, spleen and kidney had a relatively high uptake. The accumulation of radioactivity in other organs and tissues was less than 1% ID/g. The obtained results suggest that they can be used for development of radiotracer based on 68Ga and methionine for tumor imaging by PET.

Key words
Gallium-68, fluoro-18, amino acids, methionine, positron emission tomography, radiopharmaceuticals, cholangioma RS-1, radionuclide diagnostics, radiobiological effects, tumor imaging.

References

1. Granov A.M., Tyutin L.A., Stanzhevskiy A.A. Primenenie technologij yadernoj mediciny v nevrologii, psichiatrii I neirochirurgii [The application of nuclear medicine technologies in neurology, psychiatry and neurosurgery]. Vestnik RAMN – Annals of the RAMS, 2012, no. 9, pp. 13-18.

2. Petriev V.M., Tishchenko V.K., Krasikova R.N. 18F-FDG i drugie mechenye proizvodnye glukozy dlya ispolzovaniya v radionuklidnoj diagnostike onkologicheskih zabolevanij (obzor) [18F-FDG and other labeled glucose derivatives for use in radionuclide diagnosis of oncological diseases (review)]. Chimiko-pharmatsevticheskii zhournal – Pharmaceutical Chemistry Journal, 2016, vol. 50, no. 4, pp. 3-14.

3. Rösch F. Past, present and future of 68Ge/68Ga generators. Appl. Radiat. Isot., 2013, vol. 76, pp. 24-30.

4. Huang C., McConathy J. Radiolabeled amino acids for oncologic imaging. J. Nucl. Med., 2013, vol. 54, no. 7, pp. 1007-1010.

5. Zhao Y., Wang L., Pan J. The role of L-type amino acid transporter 1 in human tumors. Intractable Rare Dis. Res., 2015, vol. 4, no. 4, pp. 165-169.

6. Tlostanova M.S., Avetisyan A.O., Kozak A.R., Pishchik V.G. Klinicheskij opyt primeneniya positronno-emissionnoj tomografii s 11C-metioninom u bol’nych s vpervye vyyavlennymi obrazovaniyami v lyogkih [Clinical experience of 11С-methionine PET application for patients with first-time detected of masses in lungs]. Radiologiya – Praktika – Radiology – Practice, 2014, no. 2, pp. 26-36.

7. Kumar V., Boddeti D.K., Evans S.G., Roesch F., Howman-Giles R. Potential use of Ga-68-apotransferrin as a PET imaging agent for detecting Staphylococcus aureus infection. Nucl. Med. Biol., 2011, vol. 38, pp. 393-398.

8. Velikyan I. Prospective of 68Ga-radiopharmaceutical development. Theranostics, 2014, vol. 4, no. 1, pp. 47-80.

9. Shetty D., Jeong J.M., Ju C.H., Lee Y.S., Jeong S.Y., Choi J.Y., Yang B.Y., Lee D.S., Chung J.K., Lee M.C. Synthesis of novel 68Ga-labeled amino acid derivatives for positron emission tomography of cancer cells. Nucl. Med. Biol., 2010, vol. 37, pp. 893-902.

10. Harris S.M., Davis J.C., Snyder S.E., Butch E.R., Vavere A.L., Kocak M., Shulkin B.L. Evaluation of the biodistribution of 11C-methionine in children and young adults. J. Nucl. Med., 2013, vol. 54, no. 11, pp. 1902-1908.

11. Ono M., Oka S., Okudaira H., Schuster D.M., Goodman M.M., Kawai K., Shirakami Y. Comparative evaluation of transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid and L-[methyl-11C] methionine in human glioma cell lines. Brain Res., 2013, vol. 1535, pp. 24-37.

12. Yanagida O., Kanai Y., Chairoungdua A., Kim D.K., Segawa H., Nii T., Cha S.H., Matsuo H., Fukushima J., Fukasawa Y., Tani Y., Taketani Y., Uchino H., Kim J.Y., Inatomi J., Okayasu I., Miyamoto K., Takeda E., Goya T., Endou H. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim. Biophys. Acta, 2001, vol. 1514, no. 2, pp. 291-302.

13. Hayashi K., Anzai N. Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment. World J. Gastrointest. Oncol., 2017, vol. 9, no. 1, pp. 21-29.

14. Sakata T., Ferdous G., Tsuruta T., Satoh T., Baba S., Muto T., Ueno A., Kanai Y., Endou H., Okayasu I. L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol. Int., 2009, vol. 59, no. 1, pp. 7-18.

15. Ichinoe M., Mikami T., Yoshida T., Igawa I., Tsuruta T., Nakada N., Anzai N., Suzuki Y., Endou H., Okayasu I. High expression of L-type amino-acid transporter 1 (LAT1) in gastric carcinomas: comparison with non-cancerous lesions. Pathol. Int., 2011, vol. 61, no. 5, pp. 281-289.

16. Amano S., Inoue T., Tomiyoshi K., Ando T., Endo K. In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer. J. Nucl. Med., 1998, vol. 39, no. 8, pp. 1424-1427.

17. Toegel S., Wadsak W., Mien L.K., Viernstein H., Kluger R., Eidherr H., Haeusler D., Kletter K., Dudczak R., Mitterhauser M. Preparation and pre-vivo evaluation of no-carrier-added, carrier-added and cross-complexed [68Ga]-EDTMP formulations. Eur. J. Pharm. Biopharm., 2008, vol. 68, pp. 406-412.

18. Yano H., Shinoda J., Iwama T. Clinical Utility of Positron Emission Tomography in Patients with Malignant Glioma. Neurol. Med. Chir. (Tokyo), 2017, vol. 57, no. 7, pp. 312-320.

19. Autio A., Virtanen H., Tolvanen T., Liljenbäck H., Oikonen V., Saanijoki T., Siitonen R., Käkelä M., Schüssele A., Teräs M., Roivanen A. Absorption, distribution and excretion of intravenously injected 68Ge/68Ga generator eluate in healthy rats, and estimation of human radiation dosimetry. Eur. J. Nucl. Med. Mol. Imaging Res., 2015, vol. 5, pp. 40.

Full-text article (in Russian)