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Production and Quality Control of 225Ac-PSMA and Absorbed Dose Estimation of its in Different Human Organs

Rezazadeh Sefideh, Fatemeh | 2025

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 57849 (46)
  4. University: Sharif University of Technology
  5. Department: Energy Engineering
  6. Advisor(s): Hoseini, Abolfazl; Shirvani Arani, Simindokht; Zolghadri, Samaneh
  7. Abstract:
  8. Prostate cancer is the second leading cause of cancer-related mortality in men after lung cancer. Prostate-specific membrane antigen (PSMA-617) labeled with Actinium-225 (225Ac) is currently being studied as a potential treatment for metastatic castration-resistant prostate cancer. This study aimed to produce the labeled compound [225Ac]Ac-PSMA-617 for the treatment of prostate cancer and its metastases. The compound was synthesized under optimized labeling conditions, and its radiochemical purity was determined to be over %96 using RTLC chromatography method. The biodistribution of the compound was evaluated in the tissues of healthy male mice, and the injected activity per unit mass of tissue (%ID/g) was determined. Comparison of the biodistribution of [225Ac]Ac-PSMA-617 with free [225Ac]AcCl3 showed significant differences in tissue uptake between the two groups. Dosimetry calculations for various human organs were conducted using the MIRD method, extrapolating data from animal models to humans. S-values were calculated using the Monte Carlo MCNP code after validating it against ORNL data in three source-target organ scenarios: appropriate distance and size, complex geometric shapes and small sizes, and large distances. When the source-target organ had an appropriate distance and size, the MCNP code results closely matched the ORNL data. However, when the source organ had a complex geometric shape and the target organ was small (and vice versa), or when the distance between the source and target organs was large, slight discrepancies were observed. These differences were attributed to the different methods applied by ORNL in such conditions. The results of the biodistribution of the labeled compound [225Ac]Ac-PSMA-617 in healthy male mice showed that the highest activity accumulated in the kidneys and prostate, respectively, and the resulting dose received in human tissues related to the kidney due to the main route of excretion of radioactive substances and the presence of the PSMA receptor was 301.28 mSv/MBq, and the prostate received a dose of 160.51 mSv/MBq due to its specific membrane receptors and the specific action of this radiopharmaceutical. Initial studies on this labeled compound also indicated its high potential for use in prostate cancer treatment
  9. Keywords:
  10. Prostate Cancer ; Prostate-Specific Membrane Antigen (PSMA) ; Monte Carlo N-Particle (MCNP)Code ; Medical Internal Radiation Dose (MIRD)Method ; Actinium-225 ; Cancer Treatment

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