Radiochemical and biological assessments of a PSMA-I&S cold kit for fast and inexpensive 99mTc-labeling for SPECT imaging and radioguided surgery in prostate cancer

Frontiers in Chemistry

Chemistry

Carla Salgueiro¹  Fernanda Ferreira Mendonça²  Luciana Malavolta²  Danielle Vieira Sobral²  Lilian Yuri Itaya Yamaga³  Jorge Mejia³  Ana Claudia Ranucci Durante³  Ana Cláudia Camargo Miranda³  Marcelo Livorsi da Cunha³  Marycel Figols de Barboza³  Leonardo Lima Fuscaldi⁴  Silvia Gomez de Castiglia⁵ 

[1] Departamento de Química, Universidad Kennedy, Buenos Aires, Argentina;Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil;Hospital Israelita Albert Einstein, Sao Paulo, Brazil;Hospital Israelita Albert Einstein, Sao Paulo, Brazil;Department of Physiological Sciences, Santa Casa de Sao Paulo School of Medical Sciences, Sao Paulo, Brazil;Tecnonuclear-Eckert Ziegler, Buenos Aires, Argentina;

关键词: PSMA-I&S;    technetium-99m;    cold kits for radiopharmaceuticals;    SPECT imaging;    radioguided surgery;    prostate cancer;   

DOI  :  10.3389/fchem.2023.1271176

 received in 2023-08-01, accepted in 2023-09-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

The expression of prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer (PCa) cells and PSMA-ligands have been radiolabeled and used as radiopharmaceuticals for targeted radionuclide therapy (TRT), single photon emission computed tomography (SPECT) or positron emission tomography (PET) molecular imaging, and radioguided surgery in PCa patients. Herein, we aimed at radiolabeling the PSMA-I&S cold kit with 99mTc, resulting in a radiopharmaceutical with high radiochemical yield (RCY) and stability for SPECT imaging and radioguided surgery in PCa malignancies. Various pre-clinical assays were conducted to evaluate the [99mTc]Tc-PSMA-I&S obtained by the cold kit. These assays included assessments of RCY, radiochemical stability in saline, lipophilicity, serum protein binding (SPB), affinity for LNCaP-PCa cells (binding and internalization studies), and ex vivo biodistribution profile in naive and LNCaP-PCa-bearing mice. The radiopharmaceutical was obtained with good RCY (92.05% ± 2.20%) and remained stable for 6 h. The lipophilicity was determined to be −2.41 ± 0.06, while the SPB was ∼97%. The binding percentages to LNCaP cells were 9.41% ± 0.57% (1 h) and 10.45% ± 0.45% (4 h), with 63.12 ± 0.93 (1 h) and 65.72% ± 1.28% (4 h) of the bound material being internalized. Blocking assays, employing an excess of unlabeled PSMA-I&S, resulted in a reduction in the binding percentage by 2.6 times. The ex vivo biodistribution profile confirmed high accumulation of [99mTc]Tc-PSMA-I&S in the tumor and the tumor-to-contralateral muscle ratio was ∼6.5. In conclusion, [99mTc]Tc-PSMA-I&S was successfully obtained by radiolabeling the cold kit using freshly eluted [99mTc]NaTcO4, exhibiting good RCY and radiochemical stability. The preclinical assays demonstrated that the radiopharmaceutical shows favorable characteristics for SPECT imaging and radioguided surgery in PCa patients.

【 授权许可】

Unknown   
Copyright © 2023 Fuscaldi, Sobral, Durante, Mendonça, Miranda, Salgueiro, de Castiglia, Yamaga, da Cunha, Malavolta, de Barboza and Mejia.