Construction and Clinical Translation of ACE Targeted Nuclear Medicine Imaging Probe

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: 68Ga-DOTA-BPP; Drug: 18F-FDG

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qian Zhang; Phone Number: 13765839835; Email: 1806708691@qq.com
• Study Contact Backup: Name: Hua Zhu, M.D; Phone Number: 13671224863; Email: zhuhuabch@pku.edu

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Ethics Committee of Peking University Cancer Hospital
      • Contact: Shunlian Zhou; Email: zhoushunlian@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Study Population

Patients at Being Cancer Hospital who are confirmed TNBC.

Description

Inclusion Criteria

1. Age 18 to 75 years, inclusive; sex unrestricted.
2. 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).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Estimated life expectancy of ≥12 weeks.
5. 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 1.1.

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. Exclusion Criteria

1. 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.
2. Primary central nervous system tumors.
3. HBV DNA ≥10⁴ copies/mL or ≥2,000 IU/mL.
4. HCV RNA ≥1,000 copies/mL.
5. Positive HIV antibody or syphilis antibody test.
6. History of acute or subacute intestinal obstruction or inflammatory bowel disease.
7. Pregnancy, breastfeeding, or plans to become pregnant during the study period.
8. Known allergy to the investigational drug or any of its excipients.
9. History of substance abuse involving psychiatric medications that cannot be discontinued, or presence of a psychiatric disorder.
10. Inability to lie flat for at least 30 minutes.
11. Known allergy to any component of the imaging agents or antibodies used in the study.
12. Inability to undergo PET/CT imaging.
13. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 68Ga-DOTA-BPP; 68Ga-DOTA-BPP is an ACE1-targeted PET radiotracer. After intravenous administration of 3-5 mCi of quality-controlled 68Ga-DOTA-BPP, PET/CT imaging will be performed to evaluate the safety, biodistribution, and tumor imaging characteristics of the tracer in patients with confirmed or suspected triple-negative breast cancer.; Drug: 18F-FDG; Participants will receive an intravenous injection of 18F-FDG at 0.1-0.15 mCi/kg after fasting for at least 6 hours. Whole-body PET/CT imaging will be performed approximately 1 hour after injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of 68Ga-DOTA-BPP	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	From 68Ga-DOTA-BPP administration through completion of the PET/CT imaging procedures on the same day
Biodistribution of 68Ga-DOTA-BPP in normal organs	Visual and semiquantitative PET/CT assessment of 68Ga-DOTA-BPP uptake and distribution in normal organs at the prespecified imaging time points.	Within 2 hours after 68Ga-DOTA-BPP administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of TNBC lesions by 68Ga-DOTA-BPP PET/CT	The detection rate of target lesions by 68Ga-DOTA-BPP PET/CT will be assessed using visual and semiquantitative image analysis.	Within 2 hours after 68Ga-DOTA-BPP administration
Association between 68Ga-DOTA-BPP uptake and ACE1 expression	The relationship between tumor uptake of 68Ga-DOTA-BPP, including SUVmax, and ACE1 expression assessed by immunohistochemistry (e.g., H-score or IRS) will be evaluated in participants with available tumor tissue.	Up to 2 months after PET/CT imaging

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Estimated): December 2, 2026
• Study Completion (Estimated): December 2, 2026

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 2, 2024
• First Posted (Actual): January 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: PET/CT; diagnosis; TNBC; 68Ga labeling
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Disease; Carbohydrates; Deoxyglucose; Deoxy Sugars; Fluorodeoxyglucose F18
• Other Study ID Numbers: 2023KT160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No