Innovation Delivered

Copper‑67 radioimmunotheranostics for simultaneous immunotherapy and immuno‑SPECT

Guiyang Hao¹, Tara Mastren¹, William Silvers¹, Gedaa Hassan¹, Orhan K. Öz¹ &

Xiankai Sun^1,2

1 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

2 Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

ttps://www.nature.com/articles/s41598-021-82812-1

Introduction

Copper-67 is useful from both therapeutic and diagnostic standpoints due to its medium energy beta particle, gamma emissions, and 2.6-day half-life. Moreover, since copper radioisotopes are chemically identical, the same radiopharmaceutical can be used for ⁶⁴Cu PET imaging to pre-screen of patients and ⁶⁷Cu based radionuclide therapy. For these reasons, the usage of ⁶⁷Cu in radiotherapy has long been arisen. However until now, its widespread use has been limited by unreliable supplies, cost, and difficulty in obtaining therapeutic quantities. The recent breakthrough of copper-67 production provides an opportunity to reassess its use in radiotherapy.

Summary

In this work, Xiankai Sun and his co-workers have evaluated and demonstrated the practical use of ⁶⁷Cu in radioimmunotherapy. To demonstrate the concept, human epidermal growth factor receptor 2 (HER2) antibody, pertuzumab, was labeled with ⁶⁷Cu isotope. The radiolabeling efficiency was two-order of magnitude higher compared to literature reports. Mice bearing HER2+ xenografts showed ⁶⁷Cu-dose dependent tumor-growth inhibition from ⁶⁷Cu-labeled-Pertuzumab co-administered with trastuzumab. Moreover, authors visualized and measured [⁶⁷Cu]Cu-NOTA-Pertuzumab uptake quantitatively by SPECT imaging.

Results from nanoSPECT/CT

Thanks to technological advances of Mediso's SPECT/CT, researchers were able to perform quantitative data analysis.

• All the tumors were clearly visualized with [⁶⁷Cu]Cu-NOTA-Pertuzumab on both day 2 and day 5 post injection (Fig. 4A).
• Quantitative tumor uptake from the SPECT imaging data are presented as absolute radioactivity concentration (μCi/mL) (Fig. 4B)

Figure 4. SPECT/CT imaging results. (A) Representative maximum intensity projection (MIP)  SPECT/CT images of HCC1954 HER2+ tumor-bearing mice injected with [⁶⁷Cu]Cu-NOTA-Pertuzumab (Group 2, 3, 4, and 5) at day 2 and 5 post the start of treatment (yellow arrows indicate the tumors); (B) Actual radioactivity concentration in tumors (MBq/mL) on Day 2 and 5 (without decay correction).