Cancer Margin Detection using Infrared Spectroscopy and Plasmon Resonance

描述(申请人提供)：使用红外光谱和等离子体共振技术检测肿瘤边缘摘要虽然手术切除肿瘤组织是治疗多种形式的癌症的唯一最有效的治疗方法，但由于难以准确识别肿瘤边缘，外科手术的有效性受到限制。因此，利用体外免疫组织化学(IHC)开发肿瘤特异性分子表面探针是非常可取的。在拟议的研究中，红外(IR)光谱和表面等离子体网增强将用于评估正常组织和腺癌组织。这项技术提供了生物组织的分子特征。此外，我们将利用标记的IR报告分子系统，该分子系统由合成附着在抗肿瘤相关糖蛋白-72(抗TAG-72)上的氚化聚乙二醇分子组成，该分子选择性地与腺癌组织共定位。这解决了手术过程中正常组织和肿瘤组织之间的体外分化的关键需求。红外方法，特别是表面等离子体增强网状材料具有高度可重复性的红外吸收，有可能克服目前耗时和劳动密集型组织学方法的局限性。肿瘤边缘的特定分子特征将比目前依赖于肿瘤活检材料肉眼检查的方法更精确和可靠。先进的红外光谱分析方法可以对切除的肿瘤组织进行彻底的分析，提高手术室组织分析的质量，并指导完整的手术切除肿瘤组织。这项建议的方法是构建dPEG标记的腺癌特异性抗TAG-72单抗(MAb)，并评估这些报告程序在识别肿瘤边缘方面的使用。红外光谱和标记的抗标签单抗的结合可以减少评估时间，并向外科医生提供及时的反馈。它还可以减少对正常组织的不必要破坏或移除，改善患者的预后。抗标签单抗已被证明对结肠癌、乳腺癌和妇科癌症组织具有高度的选择性，使这种方法适用于一系列具有重要医学意义的人类癌症。在这项拟议的研究中，来自结肠、乳房和盆腔/生殖器组织的人体组织样本将由马丁、波沃斯基和奥马利博士组成的外科肿瘤学团队提供。病理小组，希区柯克和艾伦博士，将领导组织学和分析方法的发展，包括用记者构建的组织染色程序。此外，COE将领导表面等离子体红外增强方法学战略。团队成员(PI团队和外科团队)在过去几年中在MAB开发方面建立了既定的工作关系，目前的建议将IR和增强技术方面的额外专业知识结合在一起，这已证明是协同的。

DESCRIPTION (provided by applicant): Cancer Margin Detection using Infrared Spectroscopy and Plasmon Resonance Abstract While surgical resection of cancerous tissue is the single most effective treatment for many forms of human cancer, the effectiveness of surgical procedures is limited by the difficulty of accurately recognizing tumor margins. Thus, the development of cancer specific molecular surface probes using ex vivo immunohistochemistry (IHC) is highly desirable. In the proposed studies, infrared (IR) spectroscopy with surface plasmon mesh enhancement will be used to assess normal versus adenocarcinoma tissues. This technology provides molecular signatures of biological tissue. Moreover, we will utilize labeled IR reporter molecular systems that consist of deuterated polyethylene glycol (dPEG) molecules synthetically attached to anti-tumor-associated-glycoprotein- 72 (anti-TAG-72), which selectively co-locates with adenocarcinoma tissue. This addresses the critical need for ex vivo differentiation between normal and cancerous tissue during surgery. IR methods, specifically with surface plasmon enhancement mesh materials that have highly reproducible IR absorbances, have the potential to overcome the limitations of current time consuming and labor intensive histological procedures. The specific molecular characterization of tumor margins will be more precise and reliable than current methods which depend on visual inspection of tumor biopsy material. Advanced IR methods can enable thorough analysis of resected tumor tissue, increase the quality of operating room histological analyses, and guide complete surgical removal of cancerous tissue. The approach of this proposal is to construct dPEG labeled adenocarcinomo-specific anti-TAG-72 monoclonal antibodies (MAbs) and assess the use of these reporters to identify tumor margins. The combination of IR spectroscopy and labeled anti-TAG MAbs has the ability to reduce assessment time and to supply timely feedback to the surgeon. It can also reduce the needless destruction or removal of normal tissues, improving patient outcomes. Anti-TAG MAbs have been shown to be highly selective for colon, breast, and gynecological cancer tissues making this methodology applicable to a range of medically important human cancers. Human tissue samples from colon, breast and pelvic/genital tissues for this proposed research will be provided by a surgical oncology team comprised of Drs. Martin, Povoski, and O'Malley. The pathology team, Drs. Hitchcock and Allen, will lead the development of histological and analytical methods including procedures for tissue staining with reporter constructs. Additionally, Coe will lead the surface plasmon IR enhancement methodology strategies. Team members (PI team and surgical team) have an established working relationship in MAb development in past years and this current proposal brings together additional expertise in IR and enhancement technology that has shown to be synergistic.