Molecular Imaging of HER2 Expression in Breast Cancer Using [123I] I-(HE)3-G3

Overall goal of the project: To determine HER2 expression level in primary breast cancer before neoadjuvant system therapy.

Phase I. Distribution of HE3-G3 (\[123I\] I-(HE)3-G3) in patients with primary breast cancer. The study should evaluate distribution of HE3-G3 (\[123I\] I-(HE)3-G3) in patients with primary HER2-positive and HER2-negative breast cancer.

• SPECT (Drug), also known as [123I] I-(HE)3-G3: One single injection of \[123I\] I-(HE)3-G3, followed by gamma camera imaging directly postinjection and after 2, 4, 6, 24 and 48 hours.

Primary outcomes

• Gamma camera-based whole-body [123I] I-(HE)3-G3 uptake value (%) [6 hours]: Whole-body \[123I\] I-(HE)3-G3 uptake coinciding with normal organs and tissues will be assessed using gamma camera and calculated as percentage (%) of the injected dose of the radiopharmaceutical
• SPECT-based [99mTc]Tc-G3-(G3S)3C uptake value in tumor lesions (counts) [123I] I-(HE)3-G3 uptake coinciding with tumor lesions will be assessed using single-photon emission computed tomography and measured in counts [6 hours]: SPECT-based \[99mTc\]Tc-G3-(G3S)3C uptake value in tumor lesions (counts) \[123I\] I-(HE)3-G3 uptake coinciding with tumor lesions will be assessed using single-photon emission computed tomography and measured in counts
• SPECT-based [123I] I-(HE)3-G3 background uptake value (counts) [6 hours]: Focal uptake of \[123I\] I-(HE)3-G3 in the regions without pathological findings will be assessed with SPECT and measured in counts
• Tumor-to-background ratio (SPECT) [6 hours]: The SPECT-based tumor-to-background ratio will be calculated as follows: the value of \[123I\] I-(HE)3-G3 uptake coinciding with tumor lesions (counts) will be divided by the value of \[123I\] I-(HE)3-G3 uptake coinciding with the regions without pathological findings (counts)

Secondary outcomes

• Safety attributable to [123I] I-(HE)3-G3 injections (physical examination) (% of cases with abnormal findings relative to baseline) [48 hours]: The safety attributable to \[123I\] I-(HE)3-G3 injections will be evaluated based on the assessments of physical examination (% of cases with abnormal findings relative to baseline)
• Safety attributable to [123I] I-(HE)3-G3 injections (vital signs) (% of cases with abnormal findings relative to baseline) [48 hours]: The safety attributable to \[123I\] I-(HE)3-G3 injections will be evaluated based on the assessments of vital signs (% of cases with abnormal findings relative to baseline)
• Safety attributable to [123I] I-(HE)3-G3 injections (ECG) (% of cases with abnormal findings relative to baseline) [48 hours]: The safety attributable to \[123I\] I-(HE)3-G3 injections will be evaluated based on the assessments of ECG (% of cases with abnormal findings relative to baseline)
• Safety attributable to [123I] I-(HE)3-G3 injections (laboratory tests) (% of cases with abnormal findings relative to baseline) [48 hours]: The safety attributable to \[123I\] I-(HE)3-G3 injections will be evaluated based on the blood and urine laboratory tests (% of cases with abnormal findings relative to baseline)
• Safety attributable to [123I] I-(HE)3-G3 injections (% of incidence and severity of adverse events) [48 hours]: The safety attributable to \[123I\] I-(HE)3-G3 injections will be evaluated based on the rate of adverse events (%)

Sex: Female, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Subject is > 18 years of age
2. Availability of results from HER2 status previously determined on material from the primary tumor and metastatic LN, either a. HER2-positive, defined as a DAKO HercepTest™ score of 3+ or FISH positive or b. HER2-negative, defined as a DAKO HercepTest™ score of 0 or 1+; or else if 2+ then FISH negative
3. Hematological, liver and renal function test results within the following limits:

   * White blood cell count: > 2.0 x 109/L
   * Hemoglobin: > 80 g/L
   * Platelets: > 50.0 x 109/L
   * ALT, ALP, AST: =< 5.0 times Upper Limit of Normal
   * Bilirubin =< 2.0 times Upper Limit of Normal
   * Serum creatinine: Within Normal Limits
4. A negative pregnancy test for all patients of childbearing potential. Sexually active women of childbearing potential participating in the study must use a medically acceptable form of contraception for at least 30 days after study termination
5. Subject is capable to undergo the diagnostic investigations to be performed in the study
6. Informed consent

Exclusion Criteria:

1. Any system therapy (chemo-/targeted therapy)
2. Second, non-breast malignancy
3. Active current autoimmune disease or history of autoimmune disease
4. Active infection or history of severe infection within the previous 3 months (if clinically relevant at screening) 4. Known HIV positive or chronically active hepatitis B or C
5. Administration of other investigational medicinal product within 30 days of screening
6. Ongoing toxicity > grade 2 from previous standard or investigational therapies, according to US National Cancer Institute's

• Olga Bragina, Dsc, Principal investigator, Tomsk NRMC