A novel PARP inhibitor PET tracer for breast cancer

一种新型 PARP 抑制剂 PET 示踪剂用于乳腺癌

• 批准号: 10623144
• 负责人: Lilie Leming Lin
• 金额: $ 22.27万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-17 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623144
• 关键词: Aftercare; Autoradiography; BRCA mutations; Binding; Biological Assay; Biological Markers; Biopsy; Breast Cancer Patient; Breast Carcinoma; Cancer Center; Cancer-Predisposing Gene; Cells; Clinical; Clinical Management; Clinical Trials; Companions; Contralateral; DNA Repair; DNA Repair Gene; DNA Repair Pathway; DNA strand break; Data; Defect; Enrollment; Epigenetic Process; Epithelium; Event; Foundations; Gene Mutation; Genes; Genetic; Germ-Line Mutation; Goals; Human; Image; Imaging technology; Left; Malignant Neoplasms; Mass in breast; Measurement; Measures; Medical Imaging; Metastatic breast cancer; Methods; Molecular; Molecular Target; Monitor; Multicenter Trials; Mus; Muscle; Mutate; Mutation; Neoplasm Metastasis; Oral; Outcome; Ovarian Carcinoma; Patient Care; Patient Selection; Patient-Focused Outcomes; Patients; Pectoral; Pharmaceutical Preparations; Pharmacodynamics; Phase II Clinical Trials; Phenotype; Pilot Projects; Poly(ADP-ribose) Polymerase Inhibitor; Poly(ADP-ribose) Polymerases; Population; Positron-Emission Tomography; Primary Lesion; Proteins; Reproducibility; Risk; Scanning; Selection for Treatments; Signal Transduction; Spatial Distribution; Specificity; Specimen; Standardization; Technology; Testing; Therapeutic; Toxic effect; Tracer; Translations; Treatment-related toxicity; Tumor Tissue; Woman; X-Ray Computed Tomography; advanced breast cancer; cancer cell; cancer therapy; clinical imaging; cohort; drug testing; homologous recombination; imaging biomarker; improved; in vivo; malignant breast neoplasm; non-invasive imaging; novel; novel imaging technology; patient derived xenograft model; predict responsiveness; protein expression; radiotracer; real time monitoring; repaired; response; targeted agent; targeted treatment; tool; trait; tumor; tumor heterogeneity; uptake

Project Description: A novel PARP inhibitor PET tracer for breast cancer Breast cancer is the most common cancer in women, and 1 in 8 women will develop invasive breast cancer in her lifetime. Approximately 5-10% of those patients have BRCA mutations (BReast CAncer susceptibility gene). Current therapeutic strategies take advantage of the DNA repair defect in patients with BRCA mutations (BRCAMUT). By selectively targeting cancer cells rather than healthy cells, molecularly targeted agents have the potential to improve cancer outcomes and reduce toxicity compared to standard therapy. Patients who have BRCA mutations are more sensitive to PARPi. Currently, PARPi are approved for patients with metastatic germline BRCA -mutated (BRCAMUT) breast cancer. Patients with other defects in the DNA repair pathway may also benefit. Under current methods, however, which require invasive tumor biopsies, it is difficult to identify which patients may benefit as the biopsies may provide only limited information about a patient’s sensitivity to PARPi, given tumor heterogeneity and under-sampling. Furthermore, not all patients with DNA repair defects in BRCA are responsive to PARPi. Current therapeutic strategies often fail to identify the patients who are most likely to benefit. Through positron emission tomography (PET) of PARP-1 using a novel PET tracer [18F] Fluorthanatrace (FTT) that binds to activated PARP1, we can non-invasively measure PARP1 protein levels in the tumor and direct therapy to patients who are most likely to benefit from PARPi, thereby sparing those who would not benefit the unnecessary toxicities. Additionally, this novel imaging technology is low risk and can be repeated throughout treatment. Patients with locally advanced or metastatic BRCA1/2 mutated breast cancer who are enrolled on a phase II clinical trial at MD Anderson Cancer Center in which they receive PARP inhibitors will be co-enrolled on our companion imaging clinical trial of repeat [18F] FTT PET/CT imaging. [18F] FTT PET/CT will occur pretreatment and soon after PARPi initiation or twice prior to treatment initiation. Our first goal is to validate our technology for measuring PARP1 protein levels in breast cancer patients. The next goal is to demonstrate the reproducibility of our measurements in patients by having a small group undergo two scans prior to treatment. Finally, we will image a larger group of patients before treatment and then soon after treatment initiation to evaluate if PARPi reached the target. Our ultimate goal is to validate this novel imaging technology, as an early, non-invasive method to measure target engagement of PARPi in patients with metastatic germline BRCAMUT breast cancer, and thus predict responsiveness to PARPi. At the completion of this study, we will be able to confirm that this imaging technology measures PARP1 protein expression in patients and demonstrate the value of this novel imaging technology in measuring target engagement in patients receiving PARPi.

项目描述：一种新型乳腺癌PARP抑制剂PET示踪剂

项目成果

Clinical Implementation and Initial Experience With a 1.5 Tesla MR-Linac for MR-Guided Radiation Therapy for Gynecologic Cancer: An R-IDEAL Stage 1 and 2a First in Humans Feasibility Study of New Technology Implementation.

• DOI: 10.1016/j.prro.2022.03.002
• 发表时间: 2022-07
• 期刊: PRACTICAL RADIATION ONCOLOGY
• 影响因子: 3.3
• 作者: Lakomy, David S.;Yang, Jinzhong;Vedam, Sastry;Wang, Jihong;Lee, Belinda;Sobremonte, Angela;Castillo, Pamela;Hughes, Neil;Mohammedsaid, Mustefa;Jhingran, Anuja;Klopp, Ann H.;Choi, Seungtaek;Fuller, C. David;Lin, Lilie L.
• 通讯作者: Lin, Lilie L.