Studies on the adequacy of radiolabeling of PSMA-1007 with fluorine-18 - validation of analytical methodology and preclinical evaluation in the diagnosis of prostate cancer

Author(s)

Carolina Silva Ferreira dos Santos

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT)
• Defense date: 2022-01-27

Examining board members

Elaine Bortoleti de Araújo; Simone Odília Antunes Fernandes; Fabio Luiz Navarro Marques

• Advisor: Elaine Bortoleti de Araújo

Abstract

The PSMA-1007-18F is a radiotracer developed for the diagnostic procedures of prostate cancer by positron emission tomography. Because it is labeled with the fluor-18 radionuclide, which has low positron energy, it offers better image quality, and the physical half-life of 110 minutes allows transport to more distant nuclear medicine centers, these being some advantages in relation to the radiopharmaceutical PSMA-11 labeled with gallium-68. In addition, PSMA-1007-18F is mainly eliminated via the hepatobiliary route, with almost no urinary activity, providing ideal conditions for detecting focal prostate lesions. The production of PSMA-1007-18F in an automated synthesis module obtained an average labeling yield of 47.4% ± 21.5% and the analytical results showed satisfactory results, with the exception of the ethanol content in some batches. The average percentage of radiochemical purity of PSMA-1007-18F was 95.89% ± 1.32%, using aluminum-based silica gel strips for the determination of free fluorine-18 in thin layer chromatography. The validation of this analytical methodology for the determination of fluorine-18 was carried out with the radiolabeled product. The robustness of the chromatographic method used for the detection of tetrabutylammonium was demonstrated. The preclinical trials were carried out with two animal lines (BALB/c and SCID) and tumor line LNCaP cells that present PSMA receptors. In competition studies it was possible to attest the specificity of the radiopharmaceutical with high uptake in the tumor, with effective blockade of the radioactive material in 31.88%. The biodistribution and pharmacokinetics assays corroborated literature results regarding the specific binding of the radiopharmaceutical by PSMA, showing high uptake in organs that express this glycoprotein. Positron emission tomography imaging of 18F-PSMA-1007 in tumor animals with and without the presence of the competing agent PSMA I&T supports this fact. The results presented in this work will be important for the implementation of 18F-PSMA1007 production, complementing the studies in the country on this radiotracer, making its possible commercialization upon notification or registration with ANVISA. (AU)

• FAPESP's process: 19/10110-4 - Studies of adequacy of radiolabeling of PSMA-1007 with fluorine-18 : validation of the analytical methodology and pre-clinical evaluation in the diagnosis of prostate cancer
• Grantee: Carolina Silva Ferreira dos Santos
• Support Opportunities: Scholarships in Brazil - Master