National Centre for Nuclear Research, Radioisotope Centre POLATOM, 05-400 Otwock, Poland.
Molecules. 2022 Oct 25;27(21):7216. doi: 10.3390/molecules27217216.
Despite significant advances in nuclear medicine for diagnosing and treating prostate cancer (PCa), research into new ligands with increasingly better biological properties is still ongoing. Prostate-specific membrane antigen (PSMA) ligands show great potential as radioisotope carriers for the diagnosis and therapy of patients with metastatic PCa. PSMA is expressed in most types of prostate cancer, and its expression is increased in poorly differentiated, metastatic, and hormone-refractory cancers; therefore, it may be a valuable target for the development of radiopharmaceuticals and radioligands, such as urea PSMA inhibitors, for the precise diagnosis, staging, and treatment of prostate cancer. Four developed PSMA-HYNIC inhibitors for technetium-99m labeling and subsequent diagnosis were subjected to preclinical in vitro and in vivo studies to evaluate and compare their diagnostic properties. Among the studied compounds, the PSMA-T4 (Glu-CO-Lys-L-Trp-4-Amc-HYNIC) inhibitor showed the best biological properties for the diagnosis of PCa metastases. [Tc]Tc-PSMA-T4 also showed effectiveness in single-photon emission computed tomography (SPECT) studies in humans, and soon, its usefulness will be extensively evaluated in phase 2/3 clinical trials.
尽管核医学在诊断和治疗前列腺癌（PCa）方面取得了重大进展，但仍在不断研究具有更好生物学特性的新型配体。前列腺特异性膜抗原（PSMA）配体作为放射性同位素载体，在诊断和治疗转移性 PCa 患者方面具有巨大潜力。PSMA 在大多数类型的前列腺癌中表达，其在分化不良、转移性和激素难治性癌症中的表达增加；因此，它可能是开发放射性药物和放射性配体（如脲 PSMA 抑制剂）的有价值的靶点，用于前列腺癌的精确诊断、分期和治疗。四种已开发的用于锝-99m 标记和随后诊断的 PSMA-HYNIC 抑制剂进行了临床前体外和体内研究，以评估和比较它们的诊断特性。在所研究的化合物中，PSMA-T4（Glu-CO-Lys-L-Trp-4-Amc-HYNIC）抑制剂对 PCa 转移的诊断具有最佳的生物学特性。[Tc]Tc-PSMA-T4 还在单光子发射计算机断层扫描（SPECT）研究中显示出有效性，很快，其在 2/3 期临床试验中的有效性将得到广泛评估。
