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Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F.

ABSTRACT: BACKGROUND:Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing 68Ga to 18F. RESULTS:The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R2 = 0.99). 68Ga showed approximately 22 times more detectable Cerenkov signal compared to 18F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of 18F was 23.7 kBq/mL and 1.2 kBq/mL for 68Ga. The spatial resolution was 1.31 mm for 18F and 1.40 mm for 68Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. CONCLUSION:68Ga was superior over 18F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for 68Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution < 2 mm, CLI for intraoperative margin assessment using 68Ga could be feasible.

SUBMITTER: Olde Heuvel J

PROVIDER: S-EPMC6813407 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F.

Olde Heuvel J J de Wit-van der Veen B J BJ Vyas K N KN Tuch D S DS Grootendorst M R MR Stokkel M P M MPM Slump C H CH

EJNMMI physics 20191024 1

<h4>Background</h4>Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The ...[more]

PMID: 31650365

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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.

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Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F.

Publications

Performance evaluation of Cerenkov luminescence imaging: a comparison of <sup>68</sup>Ga with <sup>18</sup>F.

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