We acknowledge support from the National Cancer Institute (NCI) R01 CA128908 and Stanford Medical Scholar Research Fellowship. No other potential conflict of interest relevant to this article was reported.

1. Tumor Model
 <ol>
 <li>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.</li>
 <li>Mainta...

<ol>
	<li>Weissleder, R., Mahmood, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+imaging.">Molecular imaging.</a> Radiology. 219 (2), 316 (2001).</li><li>Chen, K., Chen, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positron+emission+tomography+imaging+of+cancer+biology:+current+status+and+future+prospects.">Positron emission tomography imaging of cancer biology: current status and future prospects.</a> Semin. Oncol. 38 (1), 70 (2011).</li><li>Solomon, M., Liu, Y., Berezin, M. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+imaging+in+cancer+research:+basic+principles,+tumor+detection,+and+therapeutic+monitoring.">Optical imaging in cancer research: basic principles, tumor detection, and therapeutic monitoring.</a> Med. Princ. Pract. 20 (5), 397 (2011).</li><li>Liu, H., Ren, G., Miao, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+Optical+Imaging+with+Radioactive+Probes.">Molecular Optical Imaging with Radioactive Probes.</a> PLoS One. 5 (3), e9470 (2010).</li><li>Robertson, R., Germanos, M. S., Li, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+imaging+of+Cerenkov+light+generation+from+positron-emitting+radiotracers.">Optical imaging of Cerenkov light generation from positron-emitting radiotracers.</a> Phys. Med. Biol. 54 (16), N355 (2009).</li><li>Xu, Y., Liu, H., Cheng, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Harnessing+the+power+of+radionuclides+for+optical+imaging:+Cerenkov+luminescence+imaging.">Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging.</a> J. Nucl. Med. 52 (12), 2009 (2011).</li><li>Cerenkov, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visible+emission+of+clean+liquids+by+action+of+g-radiation.">Visible emission of clean liquids by action of g-radiation.</a> Dokl Akad Nauk SSSR. 2, 451 (1934).</li><li>Cerenkov, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visible+radiation+produced+by+electrons+moving+in+a+medium+with+velocities+exceeding+that+of+light.">Visible radiation produced by electrons moving in a medium with velocities exceeding that of light.</a> Phys Rev. 52 (4), 0378 (1937).</li><li>Boschi, F., Calderan, L., D'Ambrosio, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+18F-FDG+tumour+uptake+measurements+in+small+animals+using+Cerenkov+radiation.">In vivo 18F-FDG tumour uptake measurements in small animals using Cerenkov radiation.</a> Eur. J. Nucl. Med. Mol. Imaging. 38 (1), 120 (2011).</li><li>Liu, H., Ren, G., Liu, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+imaging+of+reporter+gene+expression+using+a+positron-emission-tomography+probe.">Optical imaging of reporter gene expression using a positron-emission-tomography probe.</a> J. Biomed. Opt. 15 (6), 060505 (2010).</li><li>Park, J. C., Yu, M. K., An, G. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facile+preparation+of+a+hybrid+nanoprobe+for+triple-modality+optical/PET/MR+imaging.">Facile preparation of a hybrid nanoprobe for triple-modality optical/PET/MR imaging.</a> Small. 6 (24), 2863 (2010).</li><li>Xu, Y., Chang, E., Liu, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proof-of-concept+study+of+monitoring+cancer+drug+therapy+with+cerenkov+luminescence+imaging.">Proof-of-concept study of monitoring cancer drug therapy with cerenkov luminescence imaging.</a> J. Nucl. Med. 53 (2), 312 (2012).</li><li>Ellis, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bevacizumab.">Bevacizumab.</a> Nat. Rev. Drug Discov. , (2005).</li><li>Hochster, H. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bevacizumab+in+combination+with+chemotherapy:+first-line+treatment+of+patients+with+metastatic+colorectal+cancer.">Bevacizumab in combination with chemotherapy: first-line treatment of patients with metastatic colorectal cancer.</a> Semin. Oncol. 33, (2006).</li><li>Dothager, R. S., Goiffon, R. J., Jackson, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerenkov+radiation+energy+transfer+(CRET)+imaging:+a+novel+method+for+optical+imaging+of+PET+isotopes+in+biological+systems.">Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems.</a> PLoS One. 5 (10), e13300 (2010).</li><li>Hu, Z., Liang, J., Yang, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+Cerenkov+luminescence+tomography+of+the+mouse+model+with+SPECT+imaging+validation.">Experimental Cerenkov luminescence tomography of the mouse model with SPECT imaging validation.</a> Opt. Express. 18 (24), 24441 (2010).</li><li>Park, J. C., Il An, G., Park, S. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Luminescence+imaging+using+radionuclides:+a+potential+application+in+molecular+imaging.">Luminescence imaging using radionuclides: a potential application in molecular imaging.</a> Nucl. Med. Biol. 38 (3), 321 (2011).</li><li>Holland, J. P., Normand, G., Ruggiero, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+imaging+of+positron+emission+tomographic+radiotracers+using+Cerenkov+luminescence+emissions.">Intraoperative imaging of positron emission tomographic radiotracers using Cerenkov luminescence emissions.</a> Mol. Imaging. 10 (3), 177 (2011).</li><li>Liu, H., Carpenter, C. M., Jiang, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+imaging+of+tumors+using+Cerenkov+luminescence+endoscopy:+a+feasibility+experimental+study.">Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study.</a> J. Nucl. Med. , (2012).</li></ol>

No conflicts of interest declared.

CLI is emerging as a promising molecular imaging technique that has found potentials in many basic science research applications and even clinical use4,5,15,16,17. 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...

<table border="1">
 <tr>
 <td>Name</td>
 <td>Company</td>
 <td>Catalogue Number</td>
 </tr>
 <tr>
 <td>H460 Cell Line</td>
 <td>American Type Culture Collection</td>
 <td>ATCC Number: HTB-177 </td>
 </tr>
 <tr>
 <td>RPMI 1640 Medium</td>
 <td>Invitrogen Life Technologies</td>
 <td>12633-012</td>
 </tr>
 <tr>
 <td>Fetal Bovine Serum</td>
 <td>Invitrogen Life Technologies</td>
 <td>10091-148</td>
 </tr>
 <tr>
 <td>Penicillin/Streptomycin</td>
 <td>Invitrogen Life Technologies</td>
 <td>15640-055</td>
 </tr>
 <tr>
 <td>Phosphate-Buffered Saline</td>
 <td>Invitrogen Life Technologies</td>
 <td>10010-023</td>
 </tr>
 <tr>
 <td>Female Athymic Nude Mice</td>
 <td>Charles River Laboratories, Inc.</td>
 <td>Strain Code: 088</td>
 </tr>
 <tr>
 <td>Bevacizumab (Avastin)</td>
 <td>Genentech/Roche</td>
 <td>N/A</td>
 </tr>
 <tr>
 <td>MicroPET Rodent R4</td>
 <td>Siemens Medical Solutions USA, Inc.</td>
 <td>N/A</td>
 </tr>
 <tr>
 <td>Isoflurane (Aerrane)</td>
 <td>Baxter</td>
 <td>Baxter Number: AHN3637</td>
 </tr>
 <tr>
 <td>IVIS Spectrum</td>
 <td>Caliper Life Sciences</td>
 <td>N/A</td>
 </tr>
 </table>

cerenkov luminescence imaging (cli) for cancer therapy monitoring

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities1-3. 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 medium7,8. 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 others4,5,9,10,11. 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 inhibitor13,14. 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.

Watch this Scientific Journal Video about Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring at JoVE.com

Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring

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.

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

In  molecular imaging, positron emission tomography (PET) and optical imaging (OI)  are two of the most important and thus most widely used modalities1-3. ...

cerenkov-luminescence-imaging-cli-for-cancer-therapy-monitoring

Research

JoVE Journal

Medicine

13.6K Görüntüleme.  Stanford University. Preklinik kanser tedavisi izlenmesi için Cerenkov Lüminesans Görüntüleme (CLI) kullanımı burada açıklanmıştır. Bu yöntem Cerenkov Radyasyon (CR) ve radyoaktif probları görselleştirmek için optik görüntüleme (OI) yararlanır ve böylece preklinik terapötik izleme ve ilaç tarama PET için bir alternatif sunuyor.