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Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study.

ABSTRACT: Cerenkov luminescence imaging (CLI) is an emerging new molecular imaging modality that is relatively inexpensive, easy to use, and has high throughput. CLI can image clinically available PET and SPECT probes using optical instrumentation. Cerenkov luminescence endoscopy (CLE) is one of the most intriguing applications that promise potential clinical translation. We developed a prototype customized fiberscopic Cerenkov imaging system to investigate the potential in guiding minimally invasive surgical resection.All experiments were performed in a dark chamber. Cerenkov luminescence from (18)F-FDG samples containing decaying radioactivity was transmitted through an optical fiber bundle and imaged by an intensified charge-coupled device camera. Phantoms filled with (18)F-FDG were used to assess the imaging spatial resolution. Finally, mice bearing subcutaneous C6 glioma cells were injected intravenously with (18)F-FDG to determine the feasibility of in vivo imaging. The tumor tissues were exposed, and CLI was performed on the mouse before and after surgical removal of the tumor using the fiber-based imaging system and compared with a commercial optical imaging system.The sensitivity of this particular setup was approximately 45 kBq (1.21 ?Ci)/300 ?L. The 3 smallest sets of cylindric holes in a commercial SPECT phantom were identifiable via this system, demonstrating that the system has a resolution better than 1.2 mm. Finally, the in vivo tumor imaging study demonstrated the feasibility of using CLI to guide the resection of tumor tissues.This proof-of-concept study explored the feasibility of using fiber-based CLE for the detection of tumor tissue in vivo for guided surgery. With further improvements of the imaging sensitivity and spatial resolution of the current system, CLE may have a significant application in the clinical setting in the near future.

SUBMITTER: Liu H

PROVIDER: S-EPMC4887274 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study.

Liu Hongguang H Carpenter Colin M CM Jiang Han H Pratx Guillem G Sun Conroy C Buchin Michael P MP Gambhir Sanjiv S SS Xing Lei L Cheng Zhen Z

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20120817 10

<h4>Unlabelled</h4>Cerenkov luminescence imaging (CLI) is an emerging new molecular imaging modality that is relatively inexpensive, easy to use, and has high throughput. CLI can image clinically available PET and SPECT probes using optical instrumentation. Cerenkov luminescence endoscopy (CLE) is one of the most intriguing applications that promise potential clinical translation. We developed a prototype customized fiberscopic Cerenkov imaging system to investigate the potential in guiding mini ...[more]

PMID: 22904353

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Project description:The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies.In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters (18)F, (64)Cu, (89)Zr, and (124)I; beta-emitter (131)I; and alpha-particle emitter (225)Ac for potential use in CLI. The novel radiolabeled monoclonal antibody (89)Zr-desferrioxamine B [DFO]-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies.Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-, beta-, and alpha-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of (89)Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities.These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear tomographic imaging and radiotherapy have the potential to be used in CLI. The value of CLI lies in its ability to image radionuclides that do not emit either positrons or gamma-rays and are, thus, unsuitable for use with current nuclear imaging modalities. Optical imaging of Cerenkov radiation emission shows excellent promise as a potential new imaging modality for the rapid, high-throughput screening of radiopharmaceuticals.

Project description:Antibodies, and engineered antibody fragments, labeled with radioisotopes are being developed as radiotracers for the detection and phenotyping of diseases such as cancer. The development of antibody-based radiotracers requires extensive characterization of their in vitro and in vivo properties, including their ability to target tumors in an antigen-selective manner. In this study, we investigated the use of Cerenkov luminescence imaging (CLI) as compared with PET as a modality for evaluating the in vivo behavior of antibody-based radiotracers.MethodsThe anti-prostate-specific membrane antigen (PSMA) huJ591 antibody (IgG; 150 kDa) and its minibody (Mb; 80 kDa) format were functionalized with the chelator 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) and radiolabeled with the positron-emitting radionuclide 64Cu (half-life, 12.7 h). Immunoreactive preparations of the radiolabeled antibodies were injected into NCr nu/nu mice harboring PSMA-positive CWR22Rv1 and PSMA-negative PC-3 tumor xenografts. Tumor targeting was evaluated by both PET and CLI.Results64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb retained the ability to bind cell surface PSMA, and both radiotracers exhibited selective uptake into PSMA-positive tumors. Under the experimental conditions used, PSMA-selective uptake of 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb was observed by CLI as early as 3 h after injection, with tumor-to-background ratios peaking at 24 (IgG) and 16 (Mb) h after injection. Targeting data generated by CLI correlated with that generated by PET and necropsy.ConclusionCLI provided a rapid and simple assessment of the targeting specificity and pharmacokinetics of the antibody-based PET radiotracers that correlated well with the behavior observed by standard PET imaging. Moreover, CLI provided clear discrimination between uptake kinetics of an intact IgG and its small-molecular-weight derivative Mb. These data support the use of CLI for the evaluation of radiotracer performance.

Project description:Rationale: [18F]fluorodeoxyglucose-positron emission tomography ([18F]FDG-PET) has been widely used as an imaging technique to measure interscapular brown adipose tissue (iBAT) activity. However, it is challenging to obtain iBAT-specific images using [18F]FDG-PET because increased uptake of [18F]FDG is observed in tumors, muscle, and inflamed tissues. Uncoupling protein 1 (UCP1) in the mitochondrial membrane, a well-known molecular marker of BAT, has been proposed as a useful BAT imaging marker. Recently, the UCP1 ThermoMouse was developed as a reporter mouse for monitoring UCP1 expression and investigating BAT activation. In addition, Translocator protein-18 kDa (TSPO) located in the outer mitochondrial membrane is also overexpressed in BAT, suggesting that TSPO-targeting PET has potential for iBAT imaging. However, there are no studies monitoring BAT using TSPO-targeting PET probes in the UCP1 ThermoMouse. Moreover, the non-invasive Cerenkov luminescence imaging (CLI) using Cerenkov radiation from the PET probe has been proposed as an alternative option for PET as it is less expensive and user-friendly. Therefore, we selected [18F]fm-PBR28-d 2 as a TSPO-targeting PET probe for iBAT imaging to evaluate the usefulness of CLI in the UCP1 ThermoMouse. Methods: UCP1 ThermoMouse was used to monitor UCP1 expression. Western blotting and immunohistochemistry were performed to measure the level of protein expression. [18F]fm-PBR28-d 2 and [18F]FDG were used as radioactive probes for iBAT imaging. PET images were acquired with SimPET, and optical images were acquired with IVIS 100. Results: UCP1 ThermoMouse showed that UCP1 and TSPO expressions were correlated in iBAT. In both PET and CLI, the TSPO-targeting probe [18F]fm-PBR28-d 2 was superior to [18F]FDG for acquiring iBAT images. The high molar activity of the probe was essential for CLI and PET imaging. We tested the feasibility of TSPO-targeting probe under cold exposure by imaging with TSPO-PET/CLI. Both signals of iBAT were clearly increased after cold stimulation. Under prolonged isoflurane anesthesia, TSPO-targeting images showed higher signals from iBAT in the short-term than in long-term groups. Conclusion: We demonstrated that TSPO-PET/CLI reflected UCP1 expression in iBAT imaging better than [18F]FDG-PET/CLI under the various conditions. Considering convenience and cost, TSPO-CLI could be used as an alternative TSPO-PET technique for iBAT imaging.

Dataset Information

Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study.

Publications

Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study.

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