Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.
Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors.
复制标题
BLZ-100在提供自发实体瘤的荧光对比度中对荧光对比度的临床前验证。
DOI：
10.1158/0008-5472.can-15-0471
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发表时间：
2015-10-15
期刊：
影响因子：
11.2
通讯作者：
Parrish-Novak J
中科院分区：
文献类型：
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作者：
Fidel J;Kennedy KC;Dernell WS;Hansen S;Wiss V;Stroud MR;Molho JI;Knoblaugh SE;Meganck J;Olson JM;Rice B;Parrish-Novak J
肿瘤外科需要造影剂，其能够对实体肿瘤进行实时术中可视化，从而在保留周围正常组织的情况下实现完全切除。Tumor Paint™试剂BLZ - 100是一种肽 - 荧光团偶联物，能够特异性结合实体肿瘤并在近红外范围内发出荧光，最大限度地减少光散射和信号衰减。在这项研究中，我们提供了一种临床前概念验证，即对患有各种自然发生的自发性肿瘤的犬在手术前使用这种成像造影剂。对切除的组织以及部分病例在术中进行了成像。在腺癌、鳞状细胞癌、肥大细胞瘤和软组织肉瘤中，肿瘤组织与周围正常组织之间实现了可操作的对比。皮下软组织肉瘤具有最高的荧光强度和最大的肿瘤 - 背景信号比。我们的研究结果为软组织肉瘤患者的临床研究奠定了基础，软组织肉瘤是一种具有显著未满足需求的适应症。
There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint™ agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.