Evaluation of [99mTc][Tc-HYNIC/EDDA]-Tyr as a target for metabolic tumor imaging in B16F10 melanoma tumor

Document Type : Original Article

Authors

1 Department of chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran

2 Radiation Applications Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

Abstract

Objective(s): Clinical interest in metabolic imaging of cancer has been growing in recent years. The increase in protein metabolism of cancer cells is interesting target for metabolic tumor imaging, for which radiolabeled amino acids can be applied. The aim of this study was to evaluate a newly developed radiolabeled amino acid as an imaging protein metabolism in melanoma tumor.
Methods: The radiolabeled tyrosine ([99mTc][Tc-HYNIC/EDDA]-Tyr) was prepared and its biological  properties was evaluated in B16F10 melanoma tumor. Moreover organs uptake and tumor accumulation were measured in mouse bearing B16F10 melanoma tumor.
Results: Radiolabeled tyrosine was attached in B16F10 melanoma cells and showed the cell binding capacity of 13.82±0.73%. In animal study, the accumulation of radiolabeled tyrosine was observed in B16F10 melanoma tumor (2.15±0.09 %ID/g) after 30 min post injection, so that the uptake ratio of tumor to muscle was about 5.11. Through scintigraphy process the melanoma tumor clearly visualized in mice at 30 min post injection.
Conclusion: These data suggest that the novel radiotracer ([99mTc][Tc-HYNIC/EDDA]-Tyr) as an protein metabolism imaging agent, is able to transfer into melanoma cells and show great expectation for the clinical application in the imaging of melanoma tumors.

Keywords


  1. Warburg O. The metabolism of tumors. New York, NY: Richard R. Smith. 1931; 129-69.
  2. Stryer L. Amino acid degradation and the urea cycle In: Biochemistry. WH Freeman and Company, New York. 1995; 629-52.
  3. Hafliger P, Charles RP. The L-type amino acid transporter LAT1–An emerging target in cancer. Int J Mol Sci. 2019; 20:2428.
  4. Souba WW, Pacitti AJ. How amino acids get into cells: mechanisms, models, menus and J Paren Ent Nutr.1992; 16:569-78.
  5. Kawai K, Fujibayashi Y, Yonekura Y, kenichi T, hideo S, Junji K, et al. Canine SPECT studies for cerebral amino acid transport by means of 123I-3-iodo-α-methyl-l-tyrosine and preliminary kinetic analysis. Ann Nucl Med. 1995; 9:47-50.
  6. Nobusawa A, Kim M, Kaira K, Miyashita G, Negishi A, Oriuchi N, et al. Diagnostic usefulness of 18F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2013; 40:1692-1700.
  7. Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, et al. Specific transport of 3-fluoro-l-α-methyl-tyrosine by LAT1 explains its specificity to malignant tumors in imaging. Cancer Sci. 2016; 107:347-52.
  8. Achmad A, Bhattarai A, Yudistiro R, Heryanto YD, Higuchi T, Tsushima Y. The diagnostic performance of 18F-FAMT PET and 18F-FDG PET for malignancy detection: a meta-analysis. BMC Med Imaging. 2017; 17:66.
  9. Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med.1999; 40:205-12.
  10. Yaghoubi Mogadama H, Erfani M, Nikpassanda M, Mokhtary M. Preparation and assessment of a new radiotracer technetium-99m-6-hydrazinonicotinic acid-tyrosine as a targeting agent in tumor detecting through single photon emission Bioorg Chem. 2020; 104: 104181.
  11. Mazaheri Tehrani M, Erfani M, Amirmozafari N. [99mTc-HYNIC/EDDA]-MccJ25 antimicrobial peptide analog as a potential radiotracer for detection of infection. Chem Biol Drug Des. 2021; 97: 904–13.
  12. Jager PL, Vaalburg W, Pruim J, Vries E. G. E, Langen K, Piers D. A. Radiolabeled amino acids: Basic aspects and clinical applications in oncology. The journal of nuclear medicine; 2001; (42):432-45.
  13. Oda K, Hosoda N, Endo H, Saito K, Tsujihara K, Yamamura M, et al. L-type amino acid transporter 1 inhibitors inhibit tumor cell growth. Cancer Sci. 2010; 101: 173–9.
  14. Maimaiti M, Sakamoto S, Yamada Y, Sugiura M, Rii J, Takeuchi N, et al. Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma. Sci Rep. 2020; 10:1292.
  15. Wang Q, Holst J. L-type amino acid transport and cancer: targeting the mTORC1 pathway to inhibit neoplasia. Am J Cancer Res. 2015; 5:1281-94.
  16. Kaneda-Nakashima K, Zhang Z, Manabe Y,Shimoyama A, Kabayama K, Watabe T, et al. α-Emitting cancer therapy using 211At-AAMT targeting LAT1. Cancer Sci. 2021; 112:1132–40.
  17. Hayashi K, Anzai N. Novel therapeutic approaches targeting L-type amino acid transporters for cancer treatment. World J Gastrointest Oncol. 2017; 9:21–9.