Construction and Clinical Translation of ACE Targeted Nuclear Medicine Imaging Probe
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Semiquantitative assessment of lesions
研究概览
简要总结
This prospective, single-center, open-label study aims to evaluate the safety, biodistribution, and tumor imaging characteristics of the novel ACE1-targeted PET radiotracer 68Ga-DOTA-BPP in patients with confirmed or suspected triple-negative breast cancer (TNBC). Participants will undergo ^68Ga-DOTA-BPP PET/CT and 18F-FDG PET/CT. Visual and semiquantitative imaging analyses will be performed to assess tracer uptake in tumor lesions and normal organs. The relationship between ^68Ga-DOTA-BPP uptake and ACE1 expression will also be explored in participants with available tumor tissue.
详细描述
Angiotensin-converting enzyme 1 (ACE1) has been reported to be aberrantly expressed in triple-negative breast cancer (TNBC) and may represent a potential molecular imaging target. BPP is an ACE1-targeting peptide, and our group has developed 68Ga-DOTA-BPP as a novel PET radiotracer for noninvasive visualization of ACE1 expression in vivo.
This first-in-human study is designed to evaluate the safety, biodistribution, and tumor imaging characteristics of 68Ga-DOTA-BPP PET/CT in patients with confirmed or suspected TNBC. Participants will undergo 68Ga-DOTA-BPP PET/CT as well as 18F-FDG PET/CT. Visual and semiquantitative analyses will be used to characterize tracer uptake in tumor lesions and normal organs. In participants with available tumor tissue, the relationship between 68Ga-DOTA-BPP uptake and ACE1 expression assessed by immunohistochemistry will also be explored.
The study is expected to provide preliminary clinical evidence regarding the feasibility of ACE1-targeted PET imaging for the noninvasive characterization of TNBC lesions and to support further clinical development of 68Ga-DOTA-BPP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years, inclusive; sex unrestricted.
- •Patients with triple-negative breast cancer (TNBC) or suspected TNBC who are scheduled to undergo pathological tissue biopsy or surgical treatment for the tumor in the near future (within 2 months).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Estimated life expectancy of ≥12 weeks.
- •Adequate hematologic, coagulation, hepatic, and renal function, defined as follows:
- •WBC ≥4.0 × 10⁹/L or neutrophil count ≥1.5 × 10⁹/L; PLT ≥100 × 10⁹/L; Hb ≥90 g/L; PT or APTT ≤1.5 × the upper limit of normal (ULN); Total bilirubin ≤1.5 × ULN; ALT and AST ≤2.5 × ULN, or ≤5 × ULN in patients with liver metastases; ALP ≤2.5 × ULN, or ≤4.5 × ULN in patients with bone or liver metastases; BUN ≤1.5 × ULN; Serum creatinine ≤1.5 × ULN. 6:Presence of at least one measurable target lesion according to RECIST version 1.
- •7::Female participants must use effective contraceptive measures during the study period and for 6 months after completion of the study. Male participants must agree to use effective contraceptive measures during the study period and for 6 months after completion of the study.
- •8:Ability to understand the study procedures, voluntarily sign the informed consent form (ICF), and demonstrate good compliance with study requirements.
- •9:Baseline assessment established based on ^18F-FDG PET/CT findings.
排除标准
- •Presence of any of the following conditions: brain metastases, except asymptomatic primary or metastatic brain tumors that do not require treatment; carcinomatous meningitis; myocardial infarction within 6 months prior to enrollment; unstable angina; high risk of uncontrolled arrhythmia; history of coronary artery bypass grafting; cerebrovascular accident within 6 months prior to enrollment; congestive heart failure (NYHA Class III-IV); pulmonary embolism; deep vein thrombosis; concurrent infection requiring intravenous antibiotic treatment within the previous 2 weeks; or receipt of immunosuppressive therapy following organ transplantation.
- •Primary central nervous system tumors.
- •HBV DNA ≥10⁴ copies/mL or ≥2,000 IU/mL.
- •HCV RNA ≥1,000 copies/mL.
- •Positive HIV antibody or syphilis antibody test.
- •History of acute or subacute intestinal obstruction or inflammatory bowel disease.
- •Pregnancy, breastfeeding, or plans to become pregnant during the study period.
- •Known allergy to the investigational drug or any of its excipients.
- •History of substance abuse involving psychiatric medications that cannot be discontinued, or presence of a psychiatric disorder.
- •Inability to lie flat for at least 30 minutes.
- •Known allergy to any component of the imaging agents or antibodies used in the study.
- •Inability to undergo PET/CT imaging.
- •Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.
研究组 & 干预措施
68Ga-DOTA-BPP PET/CT
Participants assigned to this single arm will undergo both 18F-FDG PET/CT and 68Ga-DOTA-BPP PET/CT. 18F-FDG PET/CT will be performed as the conventional imaging examination for within-participant comparison. 68Ga-DOTA-BPP PET/CT will be performed to evaluate the safety, biodistribution, and tumor imaging characteristics of this novel ACE1-targeted radiotracer in patients with confirmed or suspected triple-negative breast cancer (TNBC). Visual and semiquantitative analyses will be used to assess radiotracer uptake in tumor lesions and normal organs.
干预措施: 68Ga-DOTA-BPP (Drug)
68Ga-DOTA-BPP PET/CT
Participants assigned to this single arm will undergo both 18F-FDG PET/CT and 68Ga-DOTA-BPP PET/CT. 18F-FDG PET/CT will be performed as the conventional imaging examination for within-participant comparison. 68Ga-DOTA-BPP PET/CT will be performed to evaluate the safety, biodistribution, and tumor imaging characteristics of this novel ACE1-targeted radiotracer in patients with confirmed or suspected triple-negative breast cancer (TNBC). Visual and semiquantitative analyses will be used to assess radiotracer uptake in tumor lesions and normal organs.
干预措施: 18F-FDG (Drug)
结局指标
主要结局
Semiquantitative assessment of lesions
时间窗: 1 year
The standardized uptake values (SUVs) of 68Ga-DOTA-BPP in lesions will be measured by the same nuclear medicine physician for all the cases
Visual assessment of lesions
时间窗: 1 year
Visual analysis of 68Ga-DOTA-BPP PET images will be performed by consensus reading by at least 2 experienced nuclear medicine physician
The biosafety, tolerability, and normal biodistribution characteristics of the 68Ga-DOTA-BPP tracer in patients with TNBC
时间窗: 1 year
Safety and tolerability of 68Ga-DOTA-BPP
时间窗: From 68Ga-DOTA-BPP administration through completion of the PET/CT imaging procedures on the same day
Incidence and severity of adverse events following intravenous administration of68Ga-DOTA-BPP, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
Biodistribution of 68Ga-DOTA-BPP in normal organs
时间窗: Within 2 hours after 68Ga-DOTA-BPP administration.
Visual and semiquantitative PET/CT assessment of 68Ga-DOTA-BPP uptake and distribution in normal organs at the prespecified imaging time points.
次要结局
- ACE expression analysis of tumor tissues(1 year)
- Correlation analysis of 68Ga-DOTA-BPP uptake and lesion size changes(1 year)
- The detection rate of 68Ga-DOTA-BPP PET/CT for target lesions in TNBC, and its concordance with the results of 18F-FDG PET/CT and immunohistochemistry (IHC).(1 year)
- Detection of TNBC lesions by 68Ga-DOTA-BPP PET/CT(Within 2 hours after 68Ga-DOTA-BPP administration)
- Association between 68Ga-DOTA-BPP uptake and ACE1 expression(Up to 2 months after PET/CT imaging)
研究者
Hua Zhu
Principal Investigator
Peking University Cancer Hospital & Institute