Improved staging of lobular breast cancer with novel amino acid metabolic and tumor neovasculature receptor imaging.

新型氨基酸代谢改善小叶性乳腺癌的分期 和肿瘤新生血管受体成像 项目摘要/摘要 浸润性小叶乳腺癌(ILC)约占乳腺恶性肿瘤的10%-15%，具有 潜在转移率高达43%。ILC生长松散，转移难以想象 使用传统的成像方式，例如计算机断层扫描(CT)、骨扫描和磁力 磁共振成像(MR)。不理想的成像对准确的分期有不利影响， 决策是有根据的。虽然氟脱氧葡萄糖(FDG)PET已被证明可以在临床上提前诊断为 当地先进的IDC，但ILC并非如此，ILC被描述为“最初懒惰，但速度很慢 循序渐进“。目前尚无准确的影像技术用于ILC的分期。我们的目标是解决 通过改进ILC的分期，特别是检测转移性疾病，未满足公共卫生需求。 氨基酸转运体在乳腺癌细胞中上调。我们和其他人已经成功地 乳腺癌用氟西洛韦(18F)PET，最初是FDA批准的合成氨基酸放射性示踪剂 在埃默里研发，用于脑胶质瘤和前列腺癌的成像。在进行的探索性研究中 埃默里和纪念斯隆-凯特林在39例乳腺癌患者(13例ILC)中的应用 在检测原发肿瘤和局部区域转移的ILC方面显示了有希望的结果。远距离 没有对疾病进行研究。 有新数据显示，使用前列腺特异性膜抗原(PSMA)正电子发射计算机断层扫描(PET)可能会改善成像效果。 乳腺癌的检测，包括ILC。前列腺特异性实际上是一个错误的词，因为PSMA受体是 在包括乳腺癌在内的许多癌症中，肿瘤新生血管表达上调。小叶的PSMA靶向 乳腺癌更有效的分期一直受到该领域专家的强烈鼓励。 我们假设，用氨基酸转运体PET进行代谢成像将改善 ILC，特别是对于远处转移，与传统成像相比。我们还假设 ILC肿瘤相关新生血管的受体导向PSMA成像将显示独特的 补充新陈代谢检查的信息，用氟西洛韦PET。 为了以最高的科学严谨性检验这些假说，我们建议对氟西洛韦进行早期试验。 和PSMA PET策略集中在利用组织学检测晚期ILC患者的转移 作为黄金标准。作为一个探索性的目标，我们还将把循环肿瘤DNA的发生联系起来。 (CtDNA)突变包括PIK3CA、ESR1、HER2和AKT1，存在转移和肿瘤负担。 我们预计这项研究将产生足够的初步数据，以确定确定NIH的可行性 受赞助的多中心试验开发更准确的分期技术以改变目前的成像实践 国际劳工组织的。

Improved staging of lobular breast cancer with novel amino acid metabolic and tumor neovasculature receptor imaging Project Summary / Abstract Invasive lobular breast cancer (ILC) accounts for approximately 10-15% of breast malignancies and has an underlying metastatic rate of up to 43%. ILC has discohesive growth making metastasis difficult to visualize with conventional imaging modalities such as computed tomography (CT), bone scan, and magnetic resonance imaging (MR). Suboptimal imaging adversely impacts accurate staging upon which therapeutic decisions are based. While fluorodeoxyglucose (FDG) PET has been shown to clinically upstage patients with locally advanced IDC, this is not so with ILC, which has been described as “initially indolent but slowly progressive”. There are no accurate imaging techniques for staging ILC. Our goal is to address an unmet public health need by improved staging of ILC, specifically detection of metastatic disease. Amino acid transporters are upregulated in breast cancer cells. We and others have successfully imaged breast cancer with fluciclovine (18F) PET, an FDA approved synthetic amino acid radiotracer originally developed at Emory for imaging of cerebral glioma and prostate cancer. In exploratory studies conducted at Emory and Memorial Sloan Kettering in 39 women with breast cancer (13 patients with ILC), fluciclovine PET demonstrated promising results in detection of ILC in primary tumors and locoregional metastases. Distant disease was not studied. There is emerging data that imaging with prostate specific membrane antigen (PSMA) PET may improve detection of breast cancer, including ILC. Prostate-specific is actually a misnomer as PSMA receptors are upregulated in tumor neovasculature in many cancers including breast cancer. PSMA targeting of lobular breast cancer for more effective staging has been strongly encouraged by experts in the field. We hypothesize that metabolic imaging with amino acid transporter PET will improve staging of ILC, particularly for distant metastases, compared to conventional imaging. We also hypothesize that receptor directed PSMA imaging of tumor associated neovasculature in ILC will reveal unique information to complement metabolic interrogation with fluciclovine PET. To test these hypotheses with the highest scientific rigor, we propose an early phase trial with fluciclovine and PSMA PET strategies centered on detection of metastasis in patients with advanced ILC using histology as the gold standard. As an exploratory aim, we will also correlate the occurrence of circulating tumor DNA (ctDNA) mutations including PIK3CA, ESR1, HER2, and AKT1 with presence of metastasis and tumor burden. We expect this study will generate sufficient preliminary data to determine feasibility for a definitive NIH sponsored multi-center trial developing more accurate staging techniques to alter current practice for imaging of ILC.