Characterizing proton-activated materials to develop PET-mediated proton range verification markers

Abstract

Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials ((18)O, Cu, and (68)Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm(-3)) and beef (~1.0 g cm(-3)) were embedded with Cu or (68)Zn foils of several volumes (10-50 mm(3)). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils' PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.

In vivo production of fluorine-18 in a chicken egg tumor model of breast cancer for proton therapy range verification

“…The use of 18-W for proton range verification was first proposed by Cho et al 21 – 23 using implantable markers or hydrogels encapsulating 18-W and its feasibility was tested in phantoms. Instead, we proposed in a previous study the direct administration of 18-W to the patient 13 .…”

“…A high concentration of the contrast in the irradiated area is required in order to provide a detectable activity that can be used for proton range verification. For this purpose, the use of 18 O-enriched water (18-W) appears as an appealing approach 22 , 23 as it is a suitable substance that can reach very high concentrations in-vivo on human tissues 24 by direct intravenous, intra-arterial or intratumoral administration to the patient. Also, the substitution of regular water by 18-W does not require to modify the treatment plan computed from a CT image of the patient, as the energy deposition and biochemical effects in the target are not affected by the isotopic distribution of its constituent atoms.…”