Human Absorbed Dose Estimation of 89Zr-Anti-HER2 Complex Based on Animal Data

Document Type : Original Paper

Authors

Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.

10.22038/ijmp.2025.78414.2386

Abstract

Introduction: This study aimed to estimate the radiation absorbed dose of human organs after injection of a high-potential PET radioimmunoconjugate of HER2+ breast cancers using the medical internal radiation dose (MIRD) method and the radiation dose assessment resource (RADAR) formalism.
Material and Methods: 89Zr was produced by the nuclear reaction of 89Y with protons (p,n), and purified by a column filled with ZR resin. The radionuclide, chemical, and radiochemical purities of the 89Zr solution were measured using gamma spectrometry, inductively coupled plasma (ICP), and radio-thin-layer chromatography (RTLC) methods, respectively. The conjugated anti-HER2 with deferoxamine (DFO) was labeled with an in-house produced 89Zr at the optimized condition to prepare 89Zr-Anti-HER2, and its radiochemical purity was assessed by the RTLC method. The stability of the radioimmunoconjugate was assessed in Phosphate-buffered saline (PBS) buffer and human serum at various intervals. Biodistribution of the final complex was studied in tumor-bearing mice at specified intervals. Finally, the absorbed dose of human organs was estimated using the MIRD method and RADAR formalism based on animal data.
Results: 89Zr radionuclide was produced by the radiochemical and radionuclide purities of >99%, and >99.99%, respectively, while the chemical impurities were < 0.1 ppm. The radiolabeled antibody was prepared with radiochemical purity >98% at optimized conditions. The results showed the liver received the maximum amount of the absorbed dose of 1.49 mGy/MBq, and other organs received < 0.87 mGy/MBq.
Conclusion: 89Zr-Anti-HER2 complex is a promising agent for PET imaging of patients with HER2+ tumors with high safety in the country.

Keywords

Main Subjects

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics. Ca Cancer J Clin. 2023 Jan 1;73(1):17-48.
  2. Wang L. Early diagnosis of breast cancer. J Sens. 2017 Jul 5;17(7):1572.
  3. Wu Y, Fu F, Meng N, Wang Z, Li X, Bai Y, et al. The role of dynamic, static, and delayed total-body PET imaging in the detection and differential diagnosis of oncological lesions. Cancer Imaging. 2024 Jan 2;24(1):2.
  4. Katal S, Eibschutz LS, Saboury B, Gholamrezanezhad A, Alavi A. Advantages and Applications of Total-Body PET Scanning. DX 2022, 12, 426.
  5. Zhang H, Zhang Z, Wang X, Wang D, Xu H, Liu Z, et al. Preparation of trastuzumab-DM1 conjugate with a high drug-to-antibod7++y ratio for breast cancer therapy. Nano Today. 2024 Feb 1; 54:102134.
  6. Ahad A, Aftab F, Michel A, Lewis JS, Contel M. Development of immunoliposomes containing cytotoxic gold payloads against HER2-positive breast cancers. RSC med chem. 2024;15(1):139-50.
  7. Shahhosseini S. PET radiopharmaceuticals. IJPR. 2011;10(1):1-2.
  8. Mohammadpour-Ghazi F, Yousefnia H, Divband G, Zolghadri S, Alirezapour B, Shakeri F. Development and evaluation of 89Zr-trastuzumab for clinical applications. AOJNMB. 2023;11(2):135.
  9. Stabin MG, Tagesson M, Thomas SR, Ljungberg M, Strand SE. Radiation dosimetry in nuclear medicine. Appl Radiat Isot. 1999 Jan 1;50(1):73-87.
  10. Yousefnia H, Zolghadri S, Jalilian AR. Preliminary Dosimetry Study of 67Ga-AATS for Human Based on Biodistribution Data in Rats. Iran J Med Phys. 2015 Jun 1;12(2):121-8.
  11. Boodaghi Malidarre R, Khabaz R, Benam MR, Zanganeh V. A feasibility study to reduce the contamination of photoneutrons and photons in organs/tissues during radiotherapy. Iran J Med Phys. 2020 Nov 1;17(6):366-73.
  12. Sina S, Naderi SM, Karimipourfard M, Molaeimanesh Z, Sadeghi M, Zamani E, et al. Development of a simple method for determining the absorbed activity concentration by the thyroid gland of nuclear medicine staff. Iran J Med Phys. 2021 May 1;18:211-7.
  13. Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. HPHY. 2003 Sep 1;85(3):294-310.
  14. Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Oak Ridge Associated Universities, TN (United States); 1999 Jan 1.
  15. Mohammadpour-Ghazi F, Yousefnia H, Zolghadri S, Yarmohammadi M, Alirezapour B, Rahiminejad A, et al. Production of radioimmunoPET grade zirconium-89. Iran J Nucl Med. 2023;31(1):20.
  16. Currie LA. Quantifying uncertainty in nuclear analytical measurements. IAEA. Sept 2004 July 1.
  17. Bolourinovin F, Mirzaei M, Faghihi R, Joharidaha F, Sina S, Hadad K, Badipa F, Yousefnia H. Preparation, quality control, biodistribution of [113mIn]In-DOTATATE. J Nuclear Sci Eng Technol. 2024; 45(3):29-35.
  18. Akbari L, Zolghadri S, Karimian A, Yousefnia H, Ranjbar S. Human absorbed dose estimation of [113mIn] In-PSMA-617 for prostate cancer imaging using animal data and Monte Carlo simulation. J Biomed Phys Eng. 2025 Aug; 20:1-0.
  19. Yousefnia H, Zolghadri S, Jalilian AR, Tajik M, Ghannadi-Maragheh M. Preliminary dosimetric evaluation of 166Ho-TTHMP for human based on biodistribution data in rats. Appl Radiat Isot. 2014 Dec 1; 94:260-5.
  20. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005 Jun 1;46(6):1023-7.
  21. O'Donoghue JA, Lewis JS, Pandit-Taskar N, Fleming SE, Schöder H, Larson SM, et al.Pharmacokinetics, biodistribution, and radiation dosimetry for 89Zr-trastuzumab in patients with esophagogastric cancer. J Nucl Med. 2018 Jan 1;59(1):161-6.
  22. Laforest R, Lapi SE, Oyama R, Bose R, Tabchy A, Marquez-Nostra BV, et al. [89 Zr] Trastuzumab: evaluation of radiation dosimetry, safety, and optimal imaging parameters in women with HER2-positive breast cancer. MIBI. 2016 Dec; 18:952-9.
  23. Shanehsazzadeh S, Yousefnia H, Lahooti A, Zolghadri S, Jalilian AR, Afarideh H. Assessment of human effective absorbed dose of 67 Ga–ECC based on biodistribution rat data. Ann Nucl Med. 2015 Feb; 29:118-24.
  24. Radiological protection in biomedical research, ICRP Publication 62 (1992).
  25. Zolghadri S, Mohammadpour-Ghazi F, Yousefnia H. Preclinical studies and absorbed dose estimation of [89Zr]Zr-DFO-Bevacizumab for PET imaging of VEGF-expressing tumors. Appl Radiat Isot. 2024 May; 28:111379.
  26. Zolghadri S, Mohammadpour-Ghazi F, Yousefnia H. Preparation, quality control, and absorbed dose estimation of 89Zr-DFO-Cetuximab for imaging of EGFR-expressing tumors. J Radioanal Nucl Chem. 2024 Apr; 26:1-0.

 

Iranian Journal of Medical Physics
Volume 22, Issue 3 - Serial Number 3
May and June 2025
Pages 203-208

Files

History

  • Receive Date: 28 February 2024
  • Revise Date: 21 July 2025
  • Accept Date: 22 July 2025

Share

How to cite

Statistics