Construction and Clinical Translation of ACE Targeted Nuclear Medicine Imaging Probe

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.

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

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.