(September 18, 2024) Gamma Eye calibration, system characterization, and in vivo imaging of 225Ac
Alpha-emitting radiopharmaceutical therapy (aRPT) has garnered increasing interest in recent years as the short path length and double DNA strand breaking power of alpha particles have the potential to kill tumor cells more effectively and selectively than beta-emitting radioisotopes.
Actinium-225 has especially gained attention as a potentially powerful therapeutic radioisotope due to several alpha-emissions in its decay chain, giving it the potential to deliver more cytotoxic dose to tumor cells than other alpha-emitters.
An unfortunate caveat to 225Ac’s tumor-killing potential is that the low administered activities in both animal models and humans limit the number of gamma rays available for imaging. The relatively low abundance of gamma rays and complex decay scheme of 225Ac, including scatter from multiple high-energy particles, further complicates 225Ac imaging. Conversely, the multiple imageable photon peaks at 440 keV (from 213Bi), 218 keV (from 221Fr), and 80-90 keV (from 213Bi, 209Tl) offer the potential to inform if and how 225Ac and its daughters accumulate differently in the body which is important for dosimetry estimates. Further, imaging of gammas resulting from aRPT administration provides the most direct information on biodistribution.
Therefore, despite its challenges, the potential information gain from 225Ac imaging makes it a worthwhile field for research & development.
In this webinar, 225Ac imaging with the Gamma Eye is explored. Calibration and system characterization procedures are described. In vivo imaging of [225Ac]DOTATATE in mice is performed at 1, 4, and 96 hours. Image data are reviewed qualitatively and quantitatively. Further, comparisons are made to in vivo imaging and cut-and-count biodistribution of [177Lu]DOTATATE. The results of this preliminary evaluation are encouraging; further testing is warranted.
Key takeaways:
- The Gamma Eye was successfully calibrated to enable 225Ac imaging.
- In vivo animal imaging enabled visualization of tumors and kidneys across multiple time points and energy windows, including generation of quantitative time-activity curves.
- While additional characterization is needed, preliminary findings encouraging for use of the Gamma Eye to test novel radiopharmaceuticals quickly and accurately in mice through direct 225Ac imaging.
About the Speaker (s)
Caitlin McCutcheon is a Senior Research Associate in the Translational Pharmacology group at Ratio Therapeutics in Boston, MA. She completed her bachelor’s degree in Biology with a Biochemistry concentration at College of the Holy Cross. She has been running all Gamma Eye studies performed at Ratio since it was installed in February of 2024.
Dr. Jacob Hesterman is the Chief Data Officer at Ratio Therapeutics. He holds degrees in Optics from the University of Rochester & University of Arizona and has almost 20 years of experience in nuclear medicine imaging hardware, reconstruction, software, image processing, and quantitation.