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 (PET) 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.

In Vivo Photoactivation Without “Light”: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light

“…Although radiation luminescence from charged particles has been used successfully for in vivo optical imaging [4,5], to the best of our knowledge, its application beyond imaging has not yet been explored. In this proof-of-concept report, we demonstrated that the phenomenon of radiation lumines- cence could be used for photoactivatable chemical conversion.…”

“…Recently, there has been growing interest in the use of photons from Cherenkov radiation for optical imaging [4][5][6][7][8][9][10][11][12] and for excitation of quantum dots and fluorophores in vivo [6,8]. Charged particles such as β + and β − which are generated from radioactive isotope decay can result in visible light with a broad energy range (ca.…”

“…When the polarized molecules relax back to the ground state, they emit light in the form of radiation luminescence. The spectrum of radiation luminescence consists of continuous wavelengths throughout the ultraviolet and visible spectrum, with the intensity distribution inversely proportional to the square of the wavelength [4,5]. The use of this light for in vivo optical imaging has, to date, been limited to the lower energy and intensity portion of the continuous spectrum.…”

Quantum Čerenkov Radiation: Spectral Cutoffs and the Role of Spin and Orbital Angular Momentum

“…Although it has been 80 years since its first observation [1], surprisingly little attention was given to the importance of the quantum nature of the charged particles producing the radiation. Since its discovery, the Čerenkov effect has become a fundamental part of many fields [2]: Devices like the ring-imaging Čerenkov detector are used for cosmic radiation measurements [3,4], while other implications also suggest novel acceleration methods [5], and even an unusual imaging tool in biology [6,7]. Because of the fundamental nature of ČR, it is found in many different physical systems, such as in nonlinear optics [8][9][10][11], it is used in the design of quantum cascade lasers [12], and it is predicted to yield the generation of entangled photon pairs [13,14].…”

Radionuclide-embedded gold nanoparticles for enhanced dendritic cell-based cancer immunotherapy, sensitive and quantitative tracking of dendritic cells with PET and Cerenkov luminescence

“…18 In this regard, Cerenkov luminescence imaging (CLI) is a promising optical-based method based on the unique property of photo-emission from luminescent radionuclides when the charged particles (mostly β + ) travel through water with velocities faster than the speed of light. 18,19 In spite of many attempts to use PET radionuclides, such as 64 Cu, 68 Ga and 124 I for CLI-based optical imaging, 20 the quantitative relationship between PET and CLI imaging has not yet been firmly established, though such knowledge is required for future CLI-based imaging in clinical applications.…”