HER2 Expression Detection and Radionuclide Therapy in Breast Cancer Using 99mTc/188Re Labeled Single Domain Antibody

Technetium-99m/Rhenium-188 Labeled Anti-HER2 Single Domain Antibody (99mTc/188Re-NM-02) for HER2 Expression Detection and Radionuclide Therapy in Breast Cancer

To evaluate the safety, dosimetry and efficacy of 99mTc/188Re labeled anti-HER2-single domain antibody (Product Code Name: 99mTc-NM-02 and 188Re-NM-02) SPECT/CT imaging of HER2 expression and radionuclide therapy in Breast Cancer. The SPECT/CT results will compare with the existing gold standard " HER2 expression detection" by biopsy tissue immunohistochemistry (IHC) and/or Fluorescence in Situ Hybridization (FISH) method, and 18F-FDG PET/CT imaging. It also to establish a new theranostic method for non-invasive HER2 expression detection and radionuclide therapy in breast cancer using 99mTc/188Re labeled anti-HER2 single domain antibody.

Anti-HER2 single domain antibody will be labeled with 99mTc and 188Re to prepare 99mTc-NM-02 and 188Re-NM-02, respectively. 99mTc-NM-02 is used as a diagnostic agent for SPECT/CT imaging of HER2 expression, and 188Re-NM-02 is used as a therapeutic drug for radionuclide therapy of HER2-postive Breast Cancer.

Inclusion Criteria:

1. Adult female, age 18 years or older
2. Prior diagnosis of breast cancer
3. Willing to participate in this study and given written informed consent
4. AST, ALT, BUN, Cr not more than double the normal values
5. Subjects of childbearing potential must be willing to undergo a pregnancy test prior to enrolment

Patients will only be included in the 188Re-NM-02 study if they meet the following supplementary criterial: HER2 postive, progression or recurrence after standard treatment, including surgery, chemotherapy, radiotherapy and targeted therapy.

Exclusion Criteria:

1. Pregnancy (subjects with a positive pregnancy test at baseline screening period or who are planning to become pregnant during the study period)
2. Breastfeeding (subjects in lactation)
3. No biopsy tissue sample can be provided for HER2 expression detection
4. Subjects with pacemakers
5. Hepatitis B virus infection (including carriers) at screening, ie hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (anti-HCV) positive, or acquired immunodeficiency disease (HIV) infected, or serum syphilis positive person
6. Abnormal liver function during baseline screening period : AST or ALT> 2 times the upper limit of normal value (ULN), if the marginal increase of a single index is judged as having no clinical significance by the investigator, it can be retested during the screening period. Once, if ≤ 2 times ULN after retesting, consider enrolling).
7. Impaired renal function during screening: serum creatinine or urea nitrogen > 1.5 times ULN.
8. Within 4 months prior to the baseline screening period , myocardial infarction or other cardiac events requiring hospitalization (unstable angina, etc.), cerebrovascular accident, transient ischemic attack, acute congestive Heart failure or severe arrhythmia (ventricular arrhythmia, atrioventricular block above II)
9. Subjects with pulmonary embolism or deep vein thrombosis
10. Various infections that the investigators consider unsuitable for study, including but not limited to patients with various infections requiring further treatment, such as urinary tract infections, respiratory infections, and diabetic foot infections.
11. Patients with abnormal thyroid function during baseline screening period (including but not limited to active hyperthyroidism, hypothyroidism or Hashimoto's thyroiditis)