Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214000, China.
Department of Urological Surgery, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214000, China.
Eur J Nucl Med Mol Imaging. 2024 Aug;51(10):2998-3008. doi: 10.1007/s00259-023-06492-x. Epub 2023 Nov 2.
Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [Ga]Ga-NYM016 for the radionuclide imaging of PCa was evaluated.
NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [Ga]Ga-NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa.
NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [Ga]Ga-NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [Ga]Ga-NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis.
The novel fluorescence probe NYM016 and the radioactive tracer [Ga]Ga-NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively.
The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.
前列腺特异性膜抗原（PSMA）是前列腺癌（PCa）有前途的诊断生物标志物。本工作设计了一种新型小分子 PSMA 靶向荧光探针 NYM016，用于 PCa 的手术导航。此外，还评估了 PET 剂 [Ga]Ga-NYM016 用于 PCa 放射性核素成像的潜力。
NYM016 设计了近红外荧光基团 Cy7 和螯合基团 NOTA。放射性探针 [Ga]Ga-NYM016 是基于 NYM016 设计和合成的。上述探针在 PSMA 阳性异种移植荷瘤模型和诊断为 PCa 的患者中进行了评估。
NYM016 在小鼠模型的肿瘤部位明显聚集，其荧光强度在 24 小时内稳定。NYM016 耐受性良好，临床研究中未发现不良反应。此外，在患有 PCa 的患者切除的病变中也观察到了 NYM016，其荧光聚集在 PSMA 高度表达的相同部位。此外，PSMA 异种移植在注射后 2.5 分钟时表现出强烈的 [Ga]Ga-NYM016 摄取。在注射后 3 小时，PSMA 异种移植的 [Ga]Ga-NYM016 摄取逐渐增加至 6.40±0.19%ID/g，高于阻断组（2.28±0.07%ID/g，P<0.05）和阴性组（2.28±0.22%ID/g，P<0.05）。在临床研究中，[Ga]Ga-NYM016 耐受性良好，未观察到不良反应。在一名复发患者的原发性和转移性病变中观察到大量摄取，最大标准化摄取值为 18.93。同时，在一名前列腺炎患者的前列腺部位观察到阴性 [Ga]Ga-NYM016 摄取。
新型荧光探针 NYM016 和放射性示踪剂 [Ga]Ga-NYM016 分别是 PCa 手术导航和放射性核素成像的有前途的候选物。
本研究的临床评估于 2022 年 12 月 21 日在 Clinicaltrial.gov（NCT05623878）注册。
