Copper‑67 radioimmunotheranostics for simultaneous immunotherapy and immuno‑SPECT
Guiyang Hao1, Tara Mastren1, William Silvers1, Gedaa Hassan1, Orhan K. Öz1 &
Xiankai Sun1,2
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.
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).