Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

Abstract

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities [1][2][3] . PET is characterized by its excellent sensitivity and quantification ability while OI is notable for non-radiation, relative low cost, short scanning time, high throughput, and wide availability to basic researchers. However, both modalities have their shortcomings as well. PET suffers from poor spatial resolution and high cost, while OI is mostly limited to preclinical applications because of its limited tissue penetration along with prominent scattering optical signals through the thickness of living tissues.Recently a bridge between PET and OI has emerged with the discovery of Cerenkov Luminescence Imaging (CLI) [4][5][6] . CLI is a new imaging modality that harnesses Cerenkov Radiation (CR) to image radionuclides with OI instruments. Russian Nobel laureate Alekseyevich Cerenkov and his colleagues originally discovered CR in 1934. It is a form of electromagnetic radiation emitted when a charged particle travels at a superluminal speed in a dielectric medium 7,8 . The charged particle, whether positron or electron, perturbs the electromagnetic field of the medium by displacing the electrons in its atoms. After passing of the disruption photons are emitted as the displaced electrons return to the ground state. For instance, one Since its emergence, CLI has been investigated for its use in a variety of preclinical applications including in vivo tumor imaging, reporter gene imaging, radiotracer development, multimodality imaging, among others 4,5,9,10,11 . The most important reason why CLI has enjoyed much success so far is that this new technology takes advantage of the low cost and wide availability of OI to image radionuclides, which used to be imaged only by more expensive and less available nuclear imaging modalities such as PET.Here, we present the method of using CLI to monitor cancer drug therapy. Our group has recently investigated this new application and validated its feasibility by a proof-of-concept study 12 . We demonstrated that CLI and PET exhibited excellent correlations across different tumor xenografts and imaging probes. This is consistent with the overarching principle of CR that CLI essentially visualizes the same radionuclides as PET. We selected Bevacizumab (Avastin; Genentech/Roche) as our therapeutic agent because it is a well-known angiogenesis inhibitor 13,14 . Maturation of this technology in the near future can be envisioned to have a significant impact on preclinical drug development, screening, as well as therapy monitoring of patients receiving treatments. Video LinkThe video component of this article can be found at http://www.jove.com/video/4341/ Protocol 1. Tumor Model 1. Culture H460 cells (American Type Culture Collection) in RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/ streptomycin (Invitrogen Life Technologies). It should be noted that the choices of cell lines, culture medium...

Quantification of Cerenkov Luminescence Imaging (CLI) Comparable With 3-D PET Standard Measurements

“…The result indicated that CLI with standard nontomography 2-D images could provide a good correlation with the 3-D tomography PET scans especially for organs located near the top surface of the mouse facing the CCD camera such as spleen. Similar other studies also confirmed the correlation of CLI with PET and its dynamic sensitivity for its capability to provide low-cost alternative to PET instrument, 12,13,15,18 which is the main driving force for many research studies on this new emerging imaging modality. According to many of these studies, CLI has a good potential for many application supplementing the high-end PET instrument.…”

Cerenkov radiation: a multi-functional approach for biological sciences

“…Subsequently, they selected Bevacizumab as a therapeutic agent to treat mice bearing H460 xenografts, and then they performed CLI and PET to monitor the therapy effect with 18 F-FLT. Excellent correlations were found between CLI and PET for the monitoring of cancer therapy [45]. Robertson et al used CLI and PET to compare the efficacy of MLN4924, a phase 2 oncology therapeutic [46].…”

Technical Note: On maximizing Cherenkov emissions from medical linear accelerators

“…Cherenkov radiation is optical light which is a natural by‐product of standard megavoltage beams for radiation therapy and has recently found applications in molecular imaging, cancer therapy monitoring, and image‐guided cancer surgery . Imaging applications specific to external beam radiation therapy have also included dose verification and entrance/exit surface dose imaging …”