Visible light modulation through radionuclides with nanoparticles

Objectives Cerenkov Luminescence (CL) is produced when a charged particle exceeds the velocity of light in a given medium. While CL has recently emerged as a new imaging modality in the preclinical space, the low photon intensity has impeded adoption and translation through the clinic. Nanoparticles (NP) however have been widely used in preclinical studies as platforms for molecular probes. Use of a higher RI medium as defined by the Frank-Tamm formula explains classically how CL flux can be increased through the use of higher velocity particles or higher RI mediums. Use of NPs represent a break from conventional theory with a heterogeneous medium and NPs have specific properties in addition to CL as defined through Frank-Tamm. Here we report the use and methods by which optically relevant NPs enhance the visible light intensity from a wide variety of CL radionuclides. Furthermore we explore visible light generation from unconventional radionuclides with low energy emitters. These fundamental methods for visible light generation expand the NP platform for CL imaging and therapeutic probes.

Methods NPs were suspended in a glucose solution to approximate the refractive index (RI) of human tissue. SPECT, PET and therapeutic β- radionuclides were mixed with NPs at a fixed activity and NP concentration. NPs tested include silica, germanium, titanium dioxide (Anatase), and other metal oxides. Visible photon flux was measured on a pre-clinical IVIS instrument to obtain total and spectral flux (500-840nm). Visible light enhancements were calculated compared to the radionuclide flux in water.

Results Using a high energy emitting radionuclide, visible photon flux ranged between 0.06 times to 5 times that of H2O with the addition of a select NP. The glucose solution alone with the high energy emitter was only 1.02 times that of H2O. Using a medium energy emitter, the visible photon flux expanded ranging from 0.02 times to 186 times that of H2O. At the extreme a low energy emitter that produced no CL in H2O yielded visible photons with the addition of NP #1. Visible photon flux enhancements of nearly 2500 times that of H2O were achieved using NP #1. Remarkably total flux for NP #1 between the lowest and highest emitter was within one log unit of luminescence. Titration of the low energy emitter show amounts as low as 1μCi can be visually detected in NP #1 (Fig. 1), opening visualization strategies for low energy radiation detection via optical imaging. Spectral analysis of the visible light flux revealed uniform enhancement by most particles, indicative of CL.

Conclusions With the increasing interest in CL for pre-clinical and clinical imaging, the need to optimize CL flux from a given radionuclide is a novel strategy for Cerenkov work. Here the use of optically relevant NPs increases the visible light flux without additional radioactivity, and with the addition of low energy emitters to the CL arsenal, new smart agents can be realized.