1. Feasibility of using O-18 for PET proton range verification
Cho JM1, Gillin M2, Ibbott GS2, Mawlawi O1.
Dept. of Imaging Physics
Dept. of Radiation Physics
MD Anderson Cancer Center
Good afternoon. I am going to talk about the feasibility of using O-18 for PET proton range verification. Since my research is a therapy-imaging hybrid, I am going to go over some basics of proton therapy. Followed by the current method of proton range verification using PET. And then, an innovation made in this research will be presented with the results of experiments I performed at Loma Linda University Proton Center and MD Anderson Cancer Center Proton Center.

2. Proton Therapy Pros Bragg Peak (BP) No distal dose Cons
Range accuracy is critical
Range uncertainty up to 10%
As you can see from the picture, x-ray beam intensity decreases with depth. Let’s say the tumor is located here. Then, x-ray radiotherapy tends to give higher dose to the normal tissue lying on top of tumor.
However, proton therapy has a great characteristic called Bragg Peak. This graph is called pristine Bragg Peak which is from a single proton beam. However, when the proton beams are modulated, we can created a nice spread out Bragg Peak as shown in this graph. This covers tumor with high dose while maintaining low surface dose. Another benefit of the proton therapy is there is no distal dose.
To take the best advantage of this Bragg Peak, we need to know the range of the proton beam quite accurately. The current CT based proton treatment plan can created up to 10% of range uncertainty in case of tissue heterogeneity. This uncertainty is not acceptable in case there is a critical organ beyond the tumor.

3. Proton range verification using PET
Planned Dose
Measured PET
I am going to talk about the current method of proton range verification using PET.
MC Dose
MC PET
Antje-Christin Knopf et al

4. Proton range verification using PET
Planned Dose
Measured PET
MC Dose
MC PET
Antje-Christin Knopf et al

5. Proton range verification using PET
Proton range verification using PET
Dose
Dose
Activity
Activity
Antje-Christin Knopf et al

6. Interaction Cross Sections in Tissue
Extremely rare isotope in the body
Litzenberg et al

7. O-18 enriched water Biologically H2O18=H2O16 Precursor for FDG
18F half-life 110 min
Extremely rare isotope in the body
Litzenberg et al

8. Measurements & Results (LLUMC)

9. Measurements & Results (MDACC)
4 different
depths
160MeV
Proton
O16 water
O18 water
Heptane
Empty
Plastic water
Depth
(cm)
% Dose
Empty C12
O18 O16

10. Measurements & Results (MDACC)
4 different
depths
160MeV
Proton
O16 water
O18 water
Heptane
Empty
Plastic water
Depth (cm)
PDD (%)
dose at depth %
Empty C12
O18 O16
96-70%
70-30%
30- 6%
15- 3%

11. Measurements & Results (MDACC)
Depth
(cm)
PDD (%)
dose at depth %
Empty C
18O O
99-87%
87-65%
65-20%
39- 8%

12. Measurements & Results (MDACC)
Depth (cm)
PDD (%)
dose at depth %
Empty C
18O O
96-70%
70-30%
30- 6%
15- 3%

13. Conclusion O-18 : strong signal at distal end.
O-18 : candidate for proton range verification using PET.

14. How to obtain O-18?
From FDG precursor
providers?
$20 ~ $100 / gram

15. How to obtain O-18? From plants? 4~10% enrichment
Natural enrichment in plant

16. Future Research Direction
Gel dosimetry study
Monte Carlo study
O-18 transport study
Animal study
Affordable O-18

17. Acknowledgement
Authors thank Dr. Schulte at Loma Linda University Medical Center and
Dr. Gonzalez-Lepera at CABIR, MD Anderson Cancer Center.
Author contact:

18. Nuclear Interactions of Protons with Tissue
4 most abundant elements
Total over 99%
6 most common interactions
16O(p,pn)15O (83.5%)
16O(p,3p4n)10C (4.2%)
16O(p,αpn)11C (2.4%)
12C(p,pn)11C (2.3%)
16O(p,p2n)14O (1.9%)
16O(p,α)13N (1.7%)
16O comprises 94 %
Muscle
Adipose
Oxygen
72.9 %
27.8 %
Carbon
12.3 %
59.8 %
Hydrogen
10.2 %
11.4 %
Nitrogen
3.5 %
0.7 %
Litzenberg et al

19. Discussion
At COM, 16O water initially gave high signal but after 20 minutes, 18O water signal was stronger.
At Distal end, 18O water was strongest over the entire time. After 20 minutes, 16O water was at noise level.
18O water shows stronger PET signals in both COM and distal end. 16O signal was noise at distal end.
Even diluted 10% 18O water gave more signal than 16O in both Gamma Camera and PET.

20. In-vivo dosimetry using PET
In-vivo dosimetry using PET
Proton beam Water in tissue Daughter product
p ~> O → O p + n
decay
15N (stable) e+
combine
e- → PET
0.511 MeV
0.511 MeV

21. Proton range verification using PET
Planned
Dose
Measured
PET
MC Dose
MC PET
Antje-Christin Knopf et al

22. Bragg-Peak Review Most protons < 10 MeV with max ~ 30 MeV
Proton at few MeV

23. Overview Proton Therapy Proton Range Verification using PET Purpose
Overview
Proton Therapy
Proton Range Verification using PET
Purpose
Properties of O-18
Method and Materials
Results
Conclusion
Future Direction

24. O-18 enriched water Biologically O-18 water = O-16 water
Precursor for FDG -18O(p,n)18F
Cross section threshold 2.6 MeV and maximum 5 MeV
18F half-life 110 min

25. O-18 enriched water Biologically O-18 water = O-16 water
Precursor for FDG -18O(p,n)18F
Cross section threshold 2.6 MeV and maximum 5 MeV
18F half-life 110 min
Litzenberg et al

26. Material and Methods

27. Results – Gamma Camera at COM

28. Results – Gamma Camera at distal end

29. Results – PET Axial COM PET axial images Distal end PET axial images
Images taken over 60 minutes
98% O18
10% O18
100% O16

30. Method & Materials (LLUMC)

31. Results (LLUMC)
98% O18
10% O18
100% O16

32. Results (MDACC)