Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Chemistry

Background:

• Copper-67 (⁶⁷Cu) offers potential for combined radionuclide therapy and SPECT imaging due to its decay properties.
• Recent advancements in ⁶⁷Cu production have renewed interest in its theranostic applications.
• Developing high-quality ⁶⁷Cu-labeled antibodies is crucial for advancing cancer radioimmunotheranostics.

Purpose of the Study:

• To assess the feasibility of creating high-quality ⁶⁷Cu-labeled antibodies for cancer radioimmunotheranostics.
• To demonstrate proof of concept using ⁶⁷Cu-labeled pertuzumab for HER2-positive breast cancer.
• To evaluate the therapeutic efficacy and imaging potential of these novel radioconjugates.

Main Methods:

• Conjugation of chelators to pertuzumab to achieve high radiolabeling efficiency.
• Preclinical therapeutic studies in mice bearing HER2⁺ xenografts using ⁶⁷Cu-labeled pertuzumab.
• Evaluation of single-photon emission computed tomography (SPECT) imaging capabilities of the ⁶⁷Cu radiopharmaceutical.

Main Results:

• Achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature.
• Demonstrated dose-dependent tumor growth inhibition of ⁶⁷Cu-labeled pertuzumab in preclinical models.
• Successfully visualized tumors using SPECT imaging with ⁶⁷Cu-labeled pertuzumab up to 5 days post-injection.

Conclusions:

• It is practical to develop ⁶⁷Cu radioimmunoconjugates for cancer radioimmunotheranostics.
• ⁶⁷Cu-labeled pertuzumab exhibits significant therapeutic potential and excellent SPECT imaging characteristics.
• This approach holds promise for improved theranostic strategies in HER2-positive cancers.