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

NCI多样性补充申请 Parent Grant：优化用于荧光引导肿瘤的氨基乙酰丙酸-原卟啉IX 切除和治疗（R15 CA 268200 -02，PI：Bin Chen） 这种多样性补充申请是为了支持乔丁奥尔森女士，在她的第一代大学毕业生 家庭，追求癌症研究的博士培训，以促进妇女和少数民族在癌症的目标 研究人员。氨基乙酰丙酸（ALA）是FDA批准的少数术中荧光探针之一 也是唯一一种基于肿瘤细胞代谢变化的分子探针。ALA在其上没有荧光， 它拥有并需要在肿瘤细胞中的血红素生物合成途径中代谢，以产生荧光和 光敏代谢物原卟啉IX（PpIX），其使得能够对肿瘤进行肿瘤荧光成像。 检测和光动力疗法（PDT）用于癌症治疗。尽管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， 肿瘤荧光的异质性高，肿瘤与正常组织的荧光对比度低。 由母基金支持的研究已经确定ABCG 2转运蛋白活性是一种关键的 降低肿瘤PpIX荧光的因子。更重要的是，我们已经确定了临床使用的药物， 抑制ABCG 2活性以增强肿瘤PpIX荧光。在这项补充研究中，乔丹将 确定ABCG 2表达的变化是否导致ALA-1中的肿瘤内和肿瘤间异质性。 PpIX荧光。此外，她还将研究肿瘤细胞中PpIX荧光异质性是否能 被ABCG 2抑制。这项拟议的研究与正在进行的工作有关， 家长补助金的资金，并将进一步扩大家长补助金的研究范围。本补充的支持 资金将使乔丹完成必要的培训，在癌症研究，使她将有 知识和技能，开始她的职业生涯作为一个癌症研究人员。

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.