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

通过新型氨基酸代谢和肿瘤新血管受体成像改善小叶乳腺癌的分期。

• 批准号: 10316260
• 负责人: David Michael Schuster
• 金额: $ 19.33万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-09 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316260
• 关键词: AKT1 gene; Address; Advocate; Amino Acid Transporter; Amino Acids; Angiogenic Factor; Antigen Receptors; Antigen Targeting; Apoptosis; Area; Attention; Autophagocytosis; Biological; Biometry; Biopsy; Blood Tests; Breast Cancer Cell; Breast Cancer Detection; Cell Cycle Progression; Cell Survival; Cerebrum; Clinical; Complement; DNA Sequence Alteration; Data; Detection; Disease; Distant; Distant Metastasis; ERBB2 gene; ESR1 gene; FDA approved; FOLH1 gene; Future; Gastrointestinal tract structure; Glioma; Goals; Gold; Growth; Histology; Image; Imaging Device; Imaging Techniques; Indolent; Leptomeninges; Lesion; Lobular; MRI Scans; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Medical Oncology; Metabolic; Modality; Molecular; Multicenter Trials; Neoplasm Metastasis; Neoplasms in Vascular Tissue; Nutrient; Oncology; PIK3CA gene; Patients; Peritoneum; Positioning Attribute; Positron-Emission Tomography; Primary Neoplasm; Prostate; Public Health; Radiation Oncology; Research; Retroperitoneal Space; Role; Signal Pathway; Signal Transduction; Staging; Surgical Oncology; Techniques; Testing; Therapeutic; Tumor Burden; United States National Institutes of Health; Universities; Vascular Endothelial Growth Factors; Vascularization; Woman; X-Ray Computed Tomography; angiogenesis; base; bone imaging; breast imaging; breast malignancies; cancer imaging; cohort; early phase trial; fluorodeoxyglucose; fluorodeoxyglucose positron emission tomography; imaging biomarker; imaging modality; improved; infiltrating duct carcinoma; malignant breast neoplasm; metabolic imaging; molecular imaging; neovasculature; novel; peripheral blood; radiotracer; receptor; standard of care; tomography; transcriptome sequencing; tumor; tumor DNA; uptake; urogenital tract

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.

利用新型氨基酸代谢改善小叶乳腺癌的分期 和肿瘤新血管受体成像 项目概要/摘要 浸润性小叶乳腺癌 (ILC) 约占乳腺恶性肿瘤的 10-15%， ILC 的潜在转移率高达 43%，具有不粘性生长，使得转移难以显现。 使用计算机断层扫描 (CT)、骨扫描和磁力扫描等传统成像方式 磁共振成像 (MR) 次优成像会对治疗的准确分期产生不利影响。 虽然氟脱氧葡萄糖 (FDG) PET 已被证明可以在临床上提高患者的分期。 本地先进的IDC，ILC却不然，被描述为“初懒而慢” 目前尚无准确的 ILC 分期成像技术，我们的目标是解决这一问题。 通过改进 ILC 分期（特别是转移性疾病的检测）来满足公共卫生需求。 我们和其他人已经成功地对乳腺癌细胞中的氨基酸转运蛋白进行了成像。 使用 Fluciclovine (18F) PET（最初是 FDA 批准的合成氨基酸放射性示踪剂）治疗乳腺癌 埃默里大学开发的用于脑胶质瘤和前列腺癌成像的探索性研究。 埃默里大学和 Memorial Sloan Kettering 医院对 39 名乳腺癌女性（13 名 ILC 患者）进行了氟西洛素 PET 治疗 在原发性肿瘤和远处转移的 ILC 检测中取得了有希望的结果。 疾病没有被研究。 新出现的数据表明，前列腺特异性膜抗原 (PSMA) PET 成像可能会改善 乳腺癌（包括 ILC）的检测实际上与 PSMA 受体一样用词不当。 在许多癌症（包括乳腺癌）的肿瘤新血管中上调。 该领域的专家强烈鼓励对乳腺癌进行更有效的分期。 我们率先使用氨基酸转运蛋白 PET 进行代谢成像，将改善癌症的分期 与传统成像相比，ILC，尤其是远处转移。 ILC 中肿瘤相关新血管的受体导向 PSMA 成像将揭示独特的 使用氟西洛素 PET 检测代谢补体的信息。 为了以最高的科学严谨性来检验这些假设，我们提出了氟西洛芬的早期试验 和 PSMA PET 策略，重点是使用组织学检测晚期 ILC 患者的转移 作为金标准，我们还将关联循环肿瘤 DNA 的发生。 (ctDNA) 突变，包括 PIK3CA、ESR1、HER2 和 AKT1，且存在转移和肿瘤负荷。 我们预计这项研究将产生足够的初步数据，以确定最终 NIH 的可行性 赞助的多中心试验开发更准确的分期技术以改变当前的成像实践 国际劳工委员会。

项目成果

Aberrant Vascular Anatomy Associated With Artifactual Focal Avidity in the Liver on PSMA PET.

PSMA PET 上与肝脏中人工局灶性亲和力相关的异常血管解剖结构。

• DOI: 10.1097/rlu.0000000000004765
• 发表时间: 2023
• 期刊: Clinical nuclear medicine
• 影响因子: 10.6
• 作者: Lawal,IsmaheelO;Pectasides,Melina;Parihar,AshwinSingh;Shah,HardikU;Halkar,RaghuveerK;Jani,AsheshB;Schuster,DavidM
• 通讯作者: Schuster,DavidM

A Tale of 3 Tracers: Contrasting Uptake Patterns of 18F-Fluciclovine, 68Ga-PSMA, and 18F-FDG in the Uterus and Adnexa.

3 种示踪剂的故事：对比 18F-Fluciclovine、68Ga-PSMA 和 18F-FDG 在子宫和附件中的摄取模式。

• DOI: 10.1097/rlu.0000000000004385
• 发表时间: 2023
• 期刊: Clinical nuclear medicine
• 影响因子: 10.6
• 作者: Lawal,IsmaheelO;Adediran,OmotayoAtinuke;Muzahir,Saima;Friend,Sarah;Bhave,ManaliAjay;Meisel,Jane;Torres,MylinA;Styblo,ToncredMarya;Graham,Cathy;Holbrook,Anna;Kalinsky,Kevin;Fielder,Bridget;Crowe,RonaldJ;Ulaner,GaryA;Schus
• 通讯作者: Schus