Review of Tissue Oxygenation Sensing During Radiotherapy Based Upon Cherenkov-Excited Luminescence Imaging

Abstract

Oxygen sensing with light has been developing for many decades using injectable molecules called Oxyphors, which are pegylated, dendrimer-encapsulated metalloporphyrins that have a phosphorescence emission lifetime that is a direct reporter of the local oxygen partial pressure (pO 2 ). In recent years, the ability to image this emission from tissue with Cherenkov light excitation during high-energy X-raybased radiation therapy has been shown and developed for research studies. The main value of this type of lifetime-based pO 2 sensing, termed Cherenkov-Excited Luminescence Imaging (CELI) is in its ability to image values of pO 2 from within the tissue during radiation therapy using tracers that are systemic and biologically compatible. Spatial mapping of pO 2 can realized either as surface imaging or deep tissue tomography through a few centimeters. The spatial resolution is radiation dose-dependent but can be near 0.1 mm, based upon radiation doses expected in a fractionated treatment plan. When imaging tumors with a broad beam irradiation, histograms of pO 2 values across the surface have been demonstrated illustrating microscopic sensitivity to the ranges of oxygen levels present, and the ability to track these microscopic histograms during daily fractionated radiation therapy is possible. The pO 2 distributions provide for sensitivity to the hypoxic fraction of the tumor-a unique capability of oxygen imaging that has microscopic spatial sampling. Comparisons of the CELI pO 2 method to other oxygen-sensing methods, as well as the ability to use the CELI technique as a tool to examine the optimization of radiation therapy treatment technique is ongoing.

Cerenkov radiation-activated probes for deep cancer theranostics: a review

“…Using X-rays to generate CR and in turn induce luminescence allows imaging at sub-millimeter resolution with nanomolar sensitivity, such as during real-time monitoring during radiotherapy in vivo [25,26]. When X-rays pass through tissues, soft collisions during energy deposition lead to de-excitation of primary or secondary electrons, generating Cerenkov emission (Figure 2A) [7]. Megavoltage X-ray radiation is an efficient CR source because the X-ray beams contain far more Cerenkov photons per electron than what traditional radionuclides generate (Figure 2B) [7].…”

“…When X-rays pass through tissues, soft collisions during energy deposition lead to de-excitation of primary or secondary electrons, generating Cerenkov emission (Figure 2A) [7]. Megavoltage X-ray radiation is an efficient CR source because the X-ray beams contain far more Cerenkov photons per electron than what traditional radionuclides generate (Figure 2B) [7]. An experimental scanning imaging system to detect CR-excited luminescence is shown in Figure 2C.…”

“…However, these methods are less effective for deep tumors because of the rapid attenuation of light as it passes through tissue [6]. To overcome this limitation, Cerenkov radiation (CR) from radionuclides and megavoltage X-ray radiation can serve as an in situ excitation source within deep tissues [7]. Blue-weighted CR occurs when a charged particle travels faster than the speed of light in a given medium [8,9].…”