(September 13, 2023) Webinar: Seeing Double: Preclinical Multiplexed PET for Dual Isotope Imaging
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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.
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(September 13, 2023) Webinar: Seeing Double: Preclinical Multiplexed PET for Dual Isotope Imaging
- 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 1) Use Standard (β+) & Non-Standard (β+γ) Radionuclides 2) Detection of Doubles and Triple Coincidences 3) 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) 82Rb 1.27 m 95 777 (13%) 52mMn 21.1 m 97 1434 (96%) 60Cu 23.7 m 93 1333 (88%) 94mTc 52.0 m 70 871 (96%) 110mIn 1.15 h 62 658 (99%) 120I 1.35 h 46 560 (72%) 44Sc 3.97 h 94 1157 (100%) 86Y 14.7 h 33 1080 (83%), 627 (33%) 76Br 16.2 h 26 559 (58%) 72As 1.08 d 88 834 (79%) 124I 4.18 d 23 602 (51%) 52Mn 5.59 d 29 744 (90%), 1434 (100%) Doubles Half-life β+ yield (%) 15O 2.04 m 100 13N 9.96 m 100 11C 20.36 m 100 68Ga 68 m 89 18F 109.7 m 97 64Cu 12.7 h 17.6 89Zr 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) 89Zr (normal) None 350-650 124I (normal) 602 350-550 86Y (normal) 627 350-550 89Zr + 124I 602 350-700 89Zr + 86Y 627 350-700 52Mn 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 0 50 100 0 50 100 150 200 % of counts used Activity of ROI [a.u.] 124I mPET 68Ga mPET 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 68Ga mPET 124I mPET 68Ga Deep-mPET 124I Deep-mPET Max Acquisition with 10% of counts Full Acquisition
- 15. Deep-mPET AI Improvements to Low Count Quantitation 0 50 100 0 50 100 150 200 % of counts used Activity of ROI [a.u.] 124I mPET 68Ga mPET 124I Deep-mPET 68Ga Deep-mPET 68Ga Deep-mPET 124I 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 RAS BRAF RAF1 MEK ERK RTK Vemurafenib Trametinib 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 1 3 1 I - T r a m e t i n i b C o l d c o l o a d e d + H e a t e d 7 0 C + 1 % B S A c o a t + 2 % B S A C o a t + 5 % B S A C o a t + 1 0 % B S A C o a t 0 10 20 30 40 % Trametinib Loaded Pratt, E.C. et al, 2023. PMID 37400715 89Zr
- 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 52Mn as a PET Radionuclide 52Mn 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 52Mn as a mPET Radionuclide 34 52Mn Courtesy of Dr. Suzanne Lapi and James Omweri (UAB) OSEM2D Reconstruction mPET Reconstruction Doubles mPET Reconstruction Triples
- 35. 52Mn Separated in mPET Phantom from 89Zr 35
- 36. Quantitation 52Mn and 89Zr ROIs 36 1 2 3 4 0 20 40 60 80 Data 1 ROI µCi per Tumor Phantom 89Zr 52Mn mPET 89Zr mPET 52Mn
- 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 INFO@SCINTICA.COM 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 0 20 40 60 0 100000 200000 300000 400000 Retention Time (minutes) Radiodetector millivolt signal [124I]I-trametinib 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-ferumoxytol [89Zr]Zr-ferumoxytol Free 89Zr [89Zr]Zr-DFO-CD39 0 10 20 30 40 0 1000 2000 3000 Retention Time (minutes) Radiotrace [86Y]Y-DOTA-PSMA 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-Oxine Free 89Zr [89Zr]Zr-Oxine [124I]I-Ly108 [124I]I-Ly108 a b c d e f 0 20 40 60 0 100000 Retention Time (minutes) Radiodetect 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-ferumoxytol [89Zr]Zr-ferumoxytol Free 89Zr 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-DFO-CD39 Free 89Zr [89Zr]Zr-DFO-CD39 0 10 20 30 40 0 1000 Retention Time (minutes) Ra 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-Oxine Free 89Zr [89Zr]Zr-Oxine 0 50 100 150 200 Position (mm) Normalized ITLC [124I]I-Ly108 [124I]I-Ly108 124I c d e f 60 utes) ib ol 0 10 20 30 40 0 1000 2000 3000 Retention Time (minutes) Radiotrace [86Y]Y-DOTA-PSMA [89Zr]Zr-Oxine b d 0 20 40 60 0 100000 Retention Time (minutes) Radiodete 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-ferumoxytol [89Zr]Zr-ferumoxytol Free 89Zr 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-DFO-CD39 Free 89Zr [89Zr]Zr-DFO-CD39 0 10 20 30 40 0 1000 Retention Time (minutes) R 0 50 100 150 200 Position (mm) Normalized ITLC [89Zr]Zr-Oxine Free 89Zr [89Zr]Zr-Oxine 0 50 100 150 200 Position (mm) Normalized ITLC [124I]I-Ly108 [124I]I-Ly108 124I c d e f Pratt, E.C. et al, 2023. PMID 37400715
Editor's Notes
- Screening of patients with the radiotracer 18FDG for example gives avidity of lesions for glucose, with typically higher avidity correlating with greater disease burden or worse prognosis. however, new lesions as well as cancers such as low-grade lung adenocarcinoma, renal cell cancer, and mucinous neoplasms are not FDG avid. A traditional FDG scan can identify only avidity. How can we multiplex PET imaging? mention compartment models, decay
- traditional PET tracks the coincidence of gammas from an annihilated positron. recontruction tracks the linear origin of the coincience. other positrons also emit a promt gamma, of an energy differing from the 511keV annihilation gammas. typically this prompt gamma is removed through software supression or narrowing of gamma energy windows. here mPET utilizes the additional gamma to distinguish it from the other positron, and a triangulation of the triple coinidence provides the origin. traditionally this prompt gamma would be considered scatter and the event removed from the reconstruction (through narrowing the energy window)
- Mention the importance of when triples are read normally they are excluded from reconstruction. why isotopes are “dirty” and not used as much compared to other “cleaner” isotopes.
- PET images have been reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF).
- NaI and transaxial. max min
- DNN net based on U-NET model with overlapping 13×13×13 voxels for training and deployment using Tensorflow or Keras Deep Neutral Net trained on reconstructed images of high and low counts to reduce bias Further refined the bilaterial filter allowing 20-fold reduction in counts Additional refinement using positron range correction to improve accuracy Unet is a convolutional neural network, skip connection for biological image processing bilateral filter is a non-linear, edge-preserving, and noise-reducing smoothing filter for images
- Mention B16F10 tumors
- Zaszczak Phantom Prompts: 522,735,872 // 703,642,993 // 856,981,955 // 14,451,883,872
- Zaszczak Phantom