Radiopharmaceutical-Free Assessment of Tumor Vasculature Condition in Particle Therapy By Means of Range-Verification PET: A Feasibility Rat Study 📝

Author: Go Akamatsu, Han Gyu Kang, Chie Seki, Hitomi Sudo, Hideaki Tashima, Chie Toramatsu, Hidekatsu Wakizaka, Iwao Yamaya, Taiga Yamaya 👨‍🔬

Affiliation: National Institutes for Quantum Science and Technology 🌍

Abstract:

Purpose:
Tumor oxygen status, which provides important information to optimize particle therapy, may constantly change during a treatment period of several weeks. However, it is impractical to perform hypoxia PET such as using 18F-FAZA for every fraction. For this issue, our hypothesis is that range-verification PET, which is based on the detection of positron (β+)-emitting nuclides produced through nuclear fragmentation reactions in tissue, may provide tumor hypoxia information. In this rat study, we compared the range-verification PET directly with 18F-FAZA PET.
Methods:
C6 glioma cancer cells were implanted into the left thigh of a nude rat. After the tumor grew in two weeks, two experiments were carried out sequentially. (a) Range-verification PET experiment: A whole tumor was irradiated with the 12C ion beam, and from PET data obtained by 30-min scan of our custom-made high-sensitivity small-animal PET system, the voxel-by-voxel washout rate constants (k2,m) were derived. (b) Hypoxia PET experiment on the next day: 18F-FAZA was injected to the same rat and hypoxia-PET imaging was performed for 30 mins.
Results:
The washout-rate image of the range-validation PET image, a k2,m image, had three regions: a faster washout rate (k2,m=∼0.26/min) mostly at the edge of the tumor, a slower washout rate (k2,m=∼0.05/min) at the core of the tumor, and a middle washout rate (k2,m=∼0.13/min) between them, which agreed with a typical structure of most solid tumors. The middle washout-rate area was consistent with the 18F-FAZA uptake, which means hypoxia. The tumor peripheral area (faster washout-rate) was considered to be a viable area with low 18F-FAZA accumulation, and the core (slower washout-rate) was considered as necrosis.
Conclusion:
The feasibility of radiopharmaceutical-free tumor imaging in carbon ion therapy by means of range-verification PET was shown by this rat irradiation study.

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