PURPOSE Aggressive variant prostate cancer (AVPC) is a nonandrogen receptor-driven form of disease that arises in men in whom standard-of-care therapies have failed. Therapeutic options for AVPC are limited, and the development of novel therapeutics is significantly hindered by the inability to accurately quantify patient response to therapy by imaging. Imaging modalities that accurately and sensitively detect the bone and visceral metastases associated with AVPC do not exist. EXPERIMENTAL DESIGN This study investigated the transmembrane protein CD133 as a targetable cell surface antigen in AVPC. We evaluated the expression of CD133 by microarray and IHC analysis. The imaging potential of the CD133-targeted IgG (HA10 IgG) was evaluated in preclinical prostate cancer models using two different imaging modalities: near-infrared and PET imaging. RESULTS Evaluation of the patient data demonstrated that CD133 is overexpressed in a specific phenotype of AVPC that is androgen receptor indifferent and neuroendocrine differentiated. In addition, HA10 IgG was selective for CD133-expressing tumors in all preclinical imaging studies. PET imaging with [89Zr]Zr-HA10 IgG revealed a mean %ID/g of 24.30 ± 3.19 in CD133-positive metastatic lesions as compared with 11.82 ± 0.57 in CD133-negative lesions after 72 hours (P = 0.0069). Ex vivo biodistribution showed similar trends as signals were increased by nearly 3-fold in CD133-positive tumors (P < 0.0001). CONCLUSIONS To our knowledge, this is the first study to define CD133 as a targetable marker of AVPC. Similarly, we have developed a novel imaging agent, which is selective for CD133-expressing tumors, resulting in a noninvasive PET imaging approach to more effectively detect and monitor AVPC.

中文翻译：

---

利用CD133进行致命性前列腺癌的靶向成像。

目的侵略性前列腺癌（AVPC）是一种非雄激素受体驱动型疾病，发生于护理标准疗法无效的男性中。AVPC的治疗选择受到限制，并且由于无法通过成像准确地量化患者对治疗的反应，因此大大阻碍了新型治疗方法的开发。不存在能够准确，灵敏地检测与AVPC相关的骨骼和内脏转移的成像方式。实验设计这项研究研究了跨膜蛋白CD133作为AVPC中可靶向的细胞表面抗原。我们通过微阵列和IHC分析评估了CD133的表达。在临床前前列腺癌模型中，使用两种不同的成像方式：近红外成像和PET成像，评估了靶向CD133的IgG（HA10 IgG）的成像潜力。结果对患者数据的评估表明CD133在AVPC的特定表型中过表达，该表型具有雄激素受体无差异和神经内分泌分化的特点。此外，在所有临床前成像研究中，HA10 IgG对表达CD133的肿瘤具有选择性。使用[89Zr] Zr-HA10 IgG的PET成像显示，CD133阳性转移灶中的平均％ID / g为24.30±3.19，而72小时后，CD133阴性转移灶中的平均％ID / g为11.82±0.57（P = 0.0069）。在CD133阳性肿瘤中，离体生物分布显示出相似的趋势，因为信号增加了近3倍（P <0.0001）。结论据我们所知，这是首次将CD133定义为AVPC的可靶向标志物的研究。同样，我们开发了一种新型的成像剂，该剂对表达CD133的肿瘤具有选择性，