Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment

NCI多样性补充申请 父母资助：用于荧光引导肿瘤的氨基酮丙酸-原卟啉IX的优化 切除和治疗(R15CA268200-02，PI：bin Chen) 这个多元化补充申请是为了支持乔丹·奥尔森女士，她是她的第一代大学毕业生 家庭，在癌症研究方面进行博士培训，目标是促进妇女和少数族裔在癌症方面的研究 研究人员。氨基乙酰丙酸(ALA)是FDA批准的为数不多的术中荧光探针之一 也是唯一基于肿瘤细胞代谢变化的分子探针。ALA上没有荧光 并需要在肿瘤细胞中的血红素生物合成途径中代谢产生一种荧光和 光敏代谢物原卟啉IX(PpIX)，使肿瘤能够进行肿瘤荧光成像 检测和光动力疗法(PDT)用于癌症治疗。虽然ALA-PPIX已在临床上使用 对于荧光引导的肿瘤切除和癌症治疗，其应用受到低肿瘤PPIX的限制 荧光，高度的肿瘤荧光异质性，以及低的肿瘤与正常组织的荧光对比度。 由父母资助的研究已经导致将ABCG2转运蛋白活性确定为关键 降低肿瘤PPIX荧光的因素。更重要的是，我们已经确定了临床上使用的药物 抑制ABCG2活性，增强肿瘤PpIX荧光。在这项补充研究中，乔丹将 确定ABCG2表达的变异是否会导致ALA肿瘤内和肿瘤间的异质性。 PPIX荧光。此外，她还将研究肿瘤细胞中的PPIX荧光异质性是否可以 通过ABCG2抑制而被抑制。这项建议的研究是与由 家长资助，并将进一步扩大家长资助的研究范围。本补充资料提供的支持 资金将使乔丁能够完成必要的癌症研究培训，以便她将拥有 作为一名癌症研究人员，她拥有开始职业生涯所需的知识和技能。

NCI Diversity Supplement Application Parent grant: Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment (R15CA268200-02, PI: Bin Chen) This diversity supplement application is to support Ms. Jordyn Olsen, a first-generation college graduate in her family, to pursue PhD training in cancer research with the goal of promoting women and minorities in cancer research workforce. Aminolevulinic acid (ALA) is one of a few FDA-approved intraoperative fluorescent probes and the only molecular probe based on the metabolic alterations in tumor cells. ALA has no fluorescence on its own and needs to be metabolized in the heme biosynthesis pathway in tumor cells to produce a fluorescent and photosensitizing metabolite protoporphyrin IX (PpIX), which enables tumor fluorescence imaging for tumor detection and photodynamic therapy (PDT) for cancer treatment. Although ALA-PpIX has been clinically used for fluorescence-guided tumor resection and cancer treatment, its applications are limited by low tumor PpIX fluorescence, high tumor fluorescence heterogeneity, and low tumor-to-normal tissue fluorescence contrast. Research supported by the parent grant has led to the identification of ABCG2 transporter activity as a critical factor in reducing tumor PpIX fluorescence. More importantly, we have identified clinically used agents to suppress ABCG2 activity to enhance tumor PpIX fluorescence. In this supplement research, Jordyn will determine whether variation in ABCG2 expression results in intra-tumor and inter-tumor heterogeneity in ALA- PpIX fluorescence. In addition, she will investigate whether PpIX fluorescence heterogeneity in tumor cells can be suppressed by ABCG2 inhibition. This proposed research is related to the on-going work supported by the parent grant funding and will further expand scope of parent grant research. Support from this supplement funding will enable Jordyn to complete the necessary training in cancer research so that she will have the knowledge and skills to start her career as a cancer researcher.