Detailed Chemistry Studies of 225Actinium Labeled Radiopharmaceuticals

Abstract

Background: The synthesis of ²²⁵Actinium derivatives was afforded by using PSMA- 617, DOTATATE peptides, and EDTMP ligand. Detailed experiments, quality control (QC), and stability studies were also well described. The radiolabelling reactions were performed in mild conditions with desirable radiochemical yields and high radiochemical purities.

Methods: PSMA-617, DOTATATE were radiolabelled with ²²⁵Actinium in 0.1 M HCl in the presence of ascorbate buffer solution and passed through the C-18 light cartridge for purification and the product was eluted by ethanol-water solution. EDTMP was also radiolabelled with ²²⁵Actinium without using any stabilizer and purification step. All products were well analyzed by R-TLC and R-HPLC. The stability of those compounds was also studied within the validity period of time.

Results: ²²⁵Ac-DOTATATE and 225Ac-PSMA-617 were obtained at the same condition. The radiochemical yield of 225Ac-DOTATATE was less than²²⁵Ac-PSMA 617. The stability experiments indicating decay daughters of ²²⁵Actinium appeared after T0 +1 h due to the recoil effect radiolysis. On the other hand, ²²⁵Ac-EDTMP was more stable than DOTA-peptide radiolabelled compounds. ²²⁵Ac-EDTMP was produced with more than 95% radiochemical yield and 99% radiochemical purity.

Conclusion: A detailed chemistry study was presented for the synthesis of ²²⁵Actinium derivatives in mild conditions with absolute radiochemical purities and high yields. The experimental results showed that ²²⁵Ac-EDTMP could be a suitable radiopharmaceutical alternative for bone metastases arising from primer tumors as a cocktail therapy.

Keywords: 225Actinium radiopharmaceuticals; EDTMP; QC; hydroxyapatite; stability; targeted alpha therapy.