The potential for Cerenkov luminescence imaging of alpha-emitting radionuclides

Abstract

Targeted α-emitting drugs are promising for cancer therapy, but cannot be effectively imaged by conventional techniques. Cerenkov luminescence imaging (CLI) has previously been shown capable of imaging β(+)- and β(-)-emitting radionuclides in vivo and could have the potential to image α-emitters. Cerenkov light production from α-emitters is through Compton scattering and from farther down the decay chain. This causes the Cerenkov production to vary in time and depend on sample geometry, complicating the interpretation of CLI images. We used the simulation toolkit Geant4 to predict the Cerenkov light output from five α-emitting radionuclides that have therapeutic potential: (225)Ac, (230)U, (213)Bi, (212)Bi and (212)At. We found that (225)Ac, (213)Bi and (212)Bi produced an order of magnitude more Cerenkov light than (18)F. However, the light from (225)Ac is delayed from the initial decay, possibly decreasing the correlation of the drug and light source. This indicates that CLI will not be helpful in the development of some α-emitting drugs.

Figure 1

Decay chains of considered isotopes. Double boxed isotopes are the starting points. Red lines indicate pathways that directly produce Cerenkov light.

Figure 2

The Monte Carlo simulation had two stages. We used Geant4 to establish the Cerenkov photon production for each isotope. Then we generated the time dependence of the Cerenkov production for the entire decay chain, using the information from the first step.

Figure 3

Average Cerenkov production for the six isotopes as predicted by Monte Carlo. Dominant sources of Cerenkov photons are annotated. Cerenkov production by ²¹¹At and ²³⁰U are 2 orders of magnitude less than ¹⁸F.

Figure 4

Cerenkov photon production rate (normalized to activity) as a function of time from a pure sample. (a) and (b) shows two different time periods for ²²⁵Ac. Note the x-axis varies in scale to account for the different half-lives of the isotopes and that the y-axis of (c) and (d) has a factor of 10⁻³.

Figure 5

Separation time for the 4 isotopes that do not only produce prompt light. Separation time represents the time between the initial decay of the parent α-emitter and the subsequent production of Cerenkov light. Note that the y-axis of (b) has a factor of 10⁻⁵.

Figure 6

The different isotopes in the decay chain are responsible for different portions of the time separation. This shows the sources of the distributions from figure 5 parts (a) and (c) on logarithmic y-axis. Vertical lines represent the delta-functions of prompt light occuring at t=0.