Treatment-induced neuroendocrine prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer. Using the ⁸⁹Zr-labeled delta-like ligand 3 (DLL3) targeting antibody SC16 (⁸⁹Zr-desferrioxamine [DFO]-SC16), we have developed a PET agent to noninvasively identify the presence of DLL3-positive NEPC lesions. Methods: Quantitative polymerase chain reaction and immunohistochemistry were used to compare relative levels of androgen receptor (AR)–regulated markers and the NEPC marker DLL3 in a panel of prostate cancer cell lines. PET imaging with ⁸⁹Zr-DFO-SC16, ⁶⁸Ga-PSMA-11, and ⁶⁸Ga-DOTATATE was performed on H660 NEPC–xenografted male nude mice. ⁸⁹Zr-DFO-SC16 uptake was corroborated by biodistribution studies. Results: In vitro studies demonstrated that H660 NEPC cells are positive for DLL3 and negative for AR, prostate-specific antigen, and prostate-specific membrane antigen (PSMA) at both the transcriptional and the translational levels. PET imaging and biodistribution studies confirmed that ⁸⁹Zr-DFO-SC16 uptake is restricted to H660 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 (⁶⁸Ga-DOTATATE). Conclusion: These studies demonstrated that H660 NEPC cells selectively express DLL3 on their cell surface and can be noninvasively identified with ⁸⁹Zr-DFO-SC16.

治疗诱发的神经内分泌前列腺癌（NEPC）是去势抵抗性前列腺癌的致命亚型。使用⁸⁹ Zr 标记的 δ 样配体 3 (DLL3) 靶向抗体 SC16（ ⁸⁹ Zr-去铁胺 [DFO]-SC16），我们开发了一种 PET 试剂，可无创地识别 DLL3 阳性 NEPC 病变的存在。方法：使用定量聚合酶链反应和免疫组织化学来比较一组前列腺癌细胞系中雄激素受体 (AR) 调节标记物和 NEPC 标记物 DLL3 的相对水平。使用⁸⁹ Zr-DFO-SC16、68 ^Ga -PSMA-11 和⁶⁸ Ga-DOTATATE 对 H660 NEPC 异种移植雄性裸鼠进行 PET 成像。 ⁸⁹ Zr-DFO-SC16 摄取已通过生物分布研究得到证实。结果：体外研究表明，H660 NEPC 细胞在转录和翻译水平上均呈 DLL3 阳性，而 AR、前列腺特异性抗原和前列腺特异性膜抗原 (PSMA) 呈阴性。 PET 成像和生物分布研究证实⁸⁹ Zr-DFO-SC16 摄取仅限于 H660 异种移植物，在非 NEPC 病变（AR 依赖性和 AR 独立性）中具有背景摄取。相反，使用靶向 PSMA ( ⁶⁸ Ga-PSMA-11) 或生长抑素受体亚型 2 ( ⁶⁸ Ga-DOTATATE) 的显像剂无法检测到 H660 异种移植物。结论：这些研究表明，H660 NEPC 细胞在其细胞表面选择性表达 DLL3，并且可以用⁸⁹ Zr-DFO-SC16 无创地识别。