Optical imaging of Cerenkov light generation from positron-emitting radiotracers

Abstract

Radiotracers labeled with high-energy positron emitters, such as those commonly used for positron emission tomography studies, emit visible light immediately following decay in a medium. This phenomenon, not previously described for these imaging tracers, is consistent with Cerenkov radiation and has several potential applications, especially for in vivo molecular imaging studies. Herein we detail a new molecular imaging tool, Cerenkov Luminescence Imaging, the experiments conducted that support our interpretation of the source of the signal, and proof-of-concept in vivo studies that set the foundation for future application of this new method.

Figure 1

The luminescence detected from well plates of 1, 10 and 100 µCi of ¹⁸F (A) or ¹³N (B) following a 10 second image acquisition. The quantification of the radiance, plotted in C, revealed that the higher energy positron-emitter produced significantly more light. For example, at 100 µCi, ¹³N produces approximately 6.5× more light than ¹⁸F.

Figure 2

A: The light output from solutions of solutions with refractive indices of approximately 1.33, 1.35, 1.37, and 1.41 (0, 10, 20, and 40% glucose) spiked with 209 µCi FDG. The light output increase as a function of glucose concentration (increase in refractive index) is consistent with the reduction in the speed of the propagation of light in the medium and an amplification of the Cerenkov radiation. B: Results from a series of filtered scans on the wavelength of light detected from positron-emitter samples. The majority of the light is produced in the blue portion of the spectrum, which is expected for Cerenkov radiation, and follows an inverse relationship with the square of the wavelength. Cerenkov light extends into the green and red region of the EM spectrum, which could increase the range of applications for in vivo imaging studies.

Figure 3

Optical scan of a mouse bearing a CWR22-RV1 xenograft following injection of 270 µCi FDG. Luminescence was detected throughout the animal, which is consistent with the broad distribution of FDG; however, for display, the image is thresholded to highlight the tumor region. In the tumor, the measured luminescence is 11× the signal measured in a region above the tumor and 47× the signal from the image background.

Figure 4

A sagittal maximum intensity projection (MIP) of an FDG PET scan on two mice bearing flank colon tumors derived from primary human tissue (A). The image were injected with 300 µCi FDG and prior to the PET scan (10 min) were imaged in the optical scanner (1 min exposure). The optical scan (Figure 4B) showed different degrees of light output that were consistent with the quantification from the PET scan. The SUV was 2.4 and 1.9, and the %ID/g was 9.8% and 7.4% (left and right, respectively). From the optical image, a similar intensity difference was measured: 4.4×10⁵ photons/s versus 2.3×10⁵ photons/s, left and right, respectively. In the optical scan, the image was thresholded to show the light emanating from the animal, demonstrating the full distribution of the FDG tracer as shown in PET scans.