(September 13, 2023) Webinar: Seeing Double: Preclinical Multiplexed PET for Dual Isotope Imaging

Overview:

In this webinar, Dr. Edwin C. Pratt discussed the realm of positron emission tomography (PET) imaging and explained the innovative concept of multiplexed PET. This new scientific advancement makes it possible to perform simultaneous imaging with two different isotopes providing more in depth information with a single scan.


Key Takeaways:

Multiplexed PET is a new reconstruction method to identify and separate positron from positron-prompt gamma emissions without new hardware from list mode PET scanners or energy discrimination of events.
Multiplexed PET is a quantitative method that is agnostic to the type of radiotracer used (IE no compartment modeling). Only a simple uniformity and sensitivity phantom is required.
Acquisition has been shown in a variety of preclinical and clinical PET scanners, though not all scanners can natively acquire data for multiplexing.
Multiplexed PET enables faster throughput for screening radiotracers, or conversely two tracer information of a tissue of interest, like imaging the tumor microenvironment for two immune populations.

1. Seeing Double: Preclinical Multiplexed PET for Dual Isotope Imaging Dr. Edwin C. Pratt Research Scholar at Memorial Sloan Kettering Cancer Center

2. Recently Published Examples of mPET 2 “Simultaneous quantitative imaging of two PET radiotracers via the detection of positron–electron annihilation and prompt gamma emissions” https://doi.org/10.1038/s41551-023-01060-y PMID: 37400715

3. PET Determines Target Avidity 3 Positron Emission Tomography (PET) Target Positive Target Negative Responder? Refractory?

4. PET vs. Multiplexed PET ( mPET ) 4 Use Standard ( β + ) & Non-Standard ( β + γ ) Radionuclides Detection of Doubles and Triple Coincidences Image Reconstruction & Separation “Doubles” “Triples” Pratt, E.C. et al, 2023. PMID 37400715

5. Standard ( β + ) and Non-Standard Radionuclides ( β + γ ) 5 Triples Half-life β + yield (%) Main Prompt γ [keV] & (β + γ / β + yield) 82 Rb 1.27 m 95 777 (13%) 52m Mn 21.1 m 97 1434 (96%) 60 Cu 23.7 m 93 1333 (88%) 94m Tc 52.0 m 70 871 (96%) 110m In 1.15 h 62 658 (99%) 120 I 1.35 h 46 560 (72%) 44 Sc 3.97 h 94 1157 (100%) 86 Y 14.7 h 33 1080 (83%), 627 (33%) 76 Br 16.2 h 26 559 (58%)  72 As 1.08 d 88 834 (79%) 124 I 4.18 d 23 602 (51%) 52 Mn 5.59 d 29 744 (90%), 1434 (100%) Doubles Half-life β + yield (%) 15 O 2.04 m 100 13 N 9.96 m 100 11 C 20.36 m 100 68 Ga 68 m 89 18 F 109.7 m 97 64 Cu 12.7 h 17.6 89 Zr 3.3 d 23 Pratt, E.C. et al, 2023. PMID 37400715

6. mPET Setup for List Mode Scanners Traditional PET: prompt gamma is “removed” favoring “doubles” mPET acquisition energy adjusted to maximize ”triples” counted 6 Scan Type Prompt Gamma (keV) Energy Window (keV) 89 Zr (normal) None 350-650 124 I (normal) 602 350-550 86 Y (normal) 627 350-550 89 Zr + 124 I 602 350-700 89 Zr + 86 Y 627 350-700 52 Mn 744 350-814* * Programmable limit of Inveon range

7. Reconstructing a Triple Event 7 Pratt, E.C. et al, 2023. PMID 37400715

8. Image Processing Workflow Comparison 8 Pratt, E.C. et al, 2023. PMID 37400715

9. Reconstructing a Triple Event 9 Pratt, E.C. et al, 2023. PMID 37400715

10. Iterations are Key for Recovery 10 Pratt, E.C. et al, 2023. PMID 37400715

11. Nearly Identical Resolution with mPET 11 Pratt, E.C. et al, 2023. PMID 37400715 Max Min

12. Reconstructing Triples are Mostly Linear 12 Pratt, E.C. et al, 2023. PMID 37400715

13. Improving Quantitative Accuracy of mPET Pratt, E.C. PMID: 37400715 Transaxial Slices 13

14. Deep-mPET uses several deep bias and noise corrections to improve low count positive bias Deep-mPET AI Improvements to Positive Bias 14 68 Ga mPET 124 I mPET 68 Ga Deep-mPET 124 I Deep-mPET Max Acquisition with 10% of counts Full Acquisition

15. Deep-mPET AI Improvements to Low Count Quantitation 68 Ga Deep-mPET 124 I Deep-mPET 15 Acquisition with 10% of counts Full Acquisition Max

16. Audience Poll

17. mPET Phantom Performance 17 Pratt, E.C. et al, 2023. PMID 37400715

18. mPET can be Quantitative 18 Pratt, E.C. et al, 2023. PMID 37400715

19. mPET Applicable to Clinical PET/CT Scanners 19 Pratt, E.C. et al, 2023. PMID 37400715

20. Tracking Small Molecules In Vivo 20 Pratt, E.C. et al, 2023. PMID 37400715

21. Can See Both Distributions with mPET 21 Pratt, E.C. et al, 2023. PMID 37400715

22. mPET is Biology Blind yet Quantitative 22 Pratt, E.C. et al, 2023. PMID 37400715

23. Drug loading with Nanoparticles 23 Pratt, E.C. et al, 2023. PMID 37400715 89 Zr

24. Nanoparticle Drug Tracking with mPET 24 Pratt, E.C. et al, 2023. PMID 37400715

25. Two Reporter System to Track CAR T-Cell Delivery Pratt, E.C. PMID: 37400715 25 Alessia Volpe

26. Two Reporter System to Track CAR T Delivery 26 Pratt, E.C. et al, 2023. PMID 37400715

27. Two Reporter System to Track CAR T Delivery 27 Pratt, E.C. et al, 2023. PMID 37400715

28. CAR-T Tracking PSMA Tumors with mPET 28 Pratt, E.C. et al, 2023. PMID 37400715

29. mPET Video CAR T-Cell Tracking 29

30. mPET for Assessing Immune Exhaustion 30

31. mPET to Track T-Cell Exhaustion 31 Pratt, E.C. et al, 2023. PMID 37400715

32. Challenges of Multiple Gamma Detection 32 Increased triple sensitivity Higher spurious background

33. Testing 52 Mn as a PET Radionuclide 52 Mn Courtesy of Dr. Suzanne Lapi and James Omweri (UAB) Energy Window 350 – 650 keV 350 – 750 keV 350 – 814 keV 350 – 814 keV Acquisition Time 10 min 10 min 10 min 4 hours Reconstruction OSEM2D OSEM2D OSEM2D OSEM2D Iterations 4 4 4 4 33

34. Testing 52 Mn as a mPET Radionuclide 34 52 Mn Courtesy of Dr. Suzanne Lapi and James Omweri (UAB) OSEM2D Reconstruction mPET Reconstruction Doubles mPET Reconstruction Triples

35. 52 Mn Separated in mPET Phantom from 89 Zr 35

36. Quantitation 52 Mn and 89 Zr ROIs 36

37. Combining Energy with mPET Sedecal SuperArgus registers list mode events with the particle energy Energy discrimination allows for higher order multiplexed PET Built in module for multiplexed PET 37 www.scintica.com

38. Antigen 3 Antigen 2 Could PET be more like Flow Cytometry? 38 PET for multiple Tracers FDG CA19.9 PSMA DLL3

39. mPET Summary Advantages: mPET is quantitative Minimal modification to list mode acquisition Increased imaging throughput per session No prior knowledge of tracer distribution needed Limitations: Rational pairing of isotopes needed Dual radiotracer production Needs a PET scanner capable of recording events in list mode 39

40. Acknowledgements Small Animal Imaging Core Dr. Suzanne Lapi (UAB) James Omweri (UAB) Funding F32 CA268912-03 P30 CA008748‑53 R01 EB033000-01 40 The Lopez- Herraiz Lab The Grimm Lab The Lewis Lab

41. Q&A Session WWW.SCINTICA.COM [email protected] Please enter your questions in the Q&A section. Thank You!

42. Orthogonal mPET CAR-T with Oxine Particle Tracking 42 Pratt, E.C. et al, 2023. PMID 37400715

43. Radiochemical Characterization Galore 43 Pratt, E.C. et al, 2023. PMID 37400715