Construction and Clinical Translation of ACE Targeted Nuclear Medicine Imaging Probe

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.

Inclusion criteria

• 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 1.
• 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 1.1.

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

• 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.