Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

Summary

Use of Cerenkov Luminescence Imaging (CLI) for monitoring preclinical cancer treatment is described here. This method takes advantage of Cerenkov Radiation (CR) and optical imaging (OI) to visualize radiolabeled probes and thus provides an alternative to PET in preclinical therapeutic monitoring and drug screening.

Abstract

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities^1-3. 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)^4-6. 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 ¹⁸F decay was estimated to produce an average of 3 photons in water⁵.

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 study¹². 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.

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 mediums, locations of inoculation, number of xenografts per mouse, and other considerations are all to be tailored to the goals of a particular study. Here we will only present one specific project design to serve as an illustration.
2. Maintain cell lines in a humidified atmosphere of 5% CO₂ at 37 °C and change to fresh medium every other day.
3. When a 75% conflue....

Discussion

CLI is emerging as a promising molecular imaging technique that has found potentials in many basic science research applications and even clinical use^4,5,15,16,17. The major advantages of CLI over traditional nuclear imaging modalities such as PET stem from its use of OI instruments, which are easier to use, characterized by short acquisition time and high throughput, significantly less expensive, and more widely available to researchers. Additionally, what sets CLI apart from OI in general is its use of.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
H460 Cell Line	American Type Culture Collection	ATCC Number: HTB-177
RPMI 1640 Medium	Invitrogen Life Technologies	12633-012
Fetal Bovine Serum	Invitrogen Life Technologies	10091-148
Penicillin/Streptomycin	Invitrogen Life Technologies	15640-055
Phosphate-Buffered Saline	Invitrogen Life Technologies	10010-023
Female Athymic Nude Mice	Charles River Laboratories, Inc.	Strain Code: 088
Bevacizumab (Avastin)	Genentech/Roche	N/A
MicroPET Rodent R4	Siemens Medical Solutions USA, Inc.	N/A
Isoflurane (Aerrane)	Baxter	Baxter Number: AHN3637
IVIS Spectrum	Caliper Life Sciences	N/A