体内分布
前列腺癌
医学
多塔
抗原
雄激素受体
癌症研究
免疫组织化学
抗体
分子成像
前列腺
化学
神经内分泌分化
内科学
癌症
谷氨酸羧肽酶Ⅱ
LNCaP公司
正电子发射断层摄影术
受体
生长抑素受体
肿瘤科
作者
Joshua Aaron Korsen,Teja Muralidhar Kalidindi,Samantha Khitrov,Zachary V. Samuels,Goutam Chakraborty,Julia A. Gutierrez,John T. Poirier,Charles M. Rudin,Juliet Chen,Michael J. Morris,Naga Vara Kishore Pillarsetty,Jason S. Lewis
标识
DOI:10.2967/jnumed.121.263221
摘要
Treatment-induced neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (CRPC). Using the zirconium-89 (89Zr)-labeled DLL3 targeting antibody SC16 (89Zr-DFO-SC16), we have developed a positron emission tomography (PET) agent to non-invasively identify the presence of DLL3-positive NEPC lesions. Methods: qPCR and immunohistochemistry were used to compare relative levels of androgen receptor (AR)-regulated markers and NEPC marker DLL3 in a panel of prostate cancer cell lines. PET imaging with 89Zr-DFO-SC16, 68Ga-PSMA-11, and 68Ga-DOTA-TATE was performed in H660 NEPC xenografted male nude mice. 89Zr-DFO-SC16 uptake was corroborated by biodistribution studies. Results: In vitro studies demonstrate H660 are positive for DLL3 and negative for AR, prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA) both at the transcriptional and translational levels. PET imaging and biodistribution studies confirm 89Zr-DFO-SC16 uptake is restricted to H660 tumor xenografts with background uptake in non-NEPC lesions (both AR-dependent and AR-independent). Conversely, H660 xenografts cannot be detected with imaging agents targeting PSMA (68Ga-PSMA-11) or somatostatin receptor subtype 2 (SSTR2) (68Ga-DOTA-TATE). Conclusion: These studies demonstrate H660 NEPC cells selectively express DLL3 on their cell surface and can be non-invasively identified with 89Zr-DFO-SC16.
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