Cerenkov-activated sticky tag for in vivo fluorescence imaging Journal Article
| Authors: | Das, S.; Haedicke, K.; Grimm, J. |
| Article Title: | Cerenkov-activated sticky tag for in vivo fluorescence imaging |
| Abstract: | A big challenge in the clinical use of Cerenkov luminescence (CL) imaging is its low signal intensity, which is several orders of magnitude below ambient light. Consequently, highly sensitive cameras, sufficient shielding from background light, and long acquisition times are required. To alleviate this problem, we hypothesized a strategy to convert the weak CL signal into a stronger fluorescence signal by using CL-activated formation of nitrenes from azides to locally fix a fluorescent probe in tissue by the formation of a covalent bond. CL-activated drug delivery was also evaluated using the same azide chemistry. The specific delivery of the CL-activated drug to cancer cells could reduce systemic toxicity, which is a limitation in chemotherapy. Methods: A cyanine-class near-infrared fluorescent dye, Cy7, and doxorubicin were synthetically attached to polyfluorinated aryl azide to form Cy7 azide and DOX azide, respectively. Fibrosarcoma cells were incubated with 18F-FDG and exposed to Cy7 azide with subsequent fluorescence imaging. For CL-activated tagging in vivo, tumor-bearing mice were injected first with 90Y-DOTA-RGD, targeting avb3 integrins, and then with the Cy7 azide. Fluorescence signal was imaged over time. Breast cancer cells were incubated with DOX azide and 68Ga, after which cell viability was quantified using an assay. Results: CL photoactivation of Cy7 azide in vitro showed significantly higher fluorescence signal from 18F-FDG–treated than untreated cells. In vivo, CL photoactivation could be shown by using the tumor-specific, integrin-targeting 90Y-DOTA-RGD and the localized activation of Cy7 azide. Here, localized CL-induced fluorescence was detected in the tumors and remained significantly higher over several days than in tumors without CL. We also established as a next step CL-activated drug delivery of DOX azide by showing significantly decreasing cell viability of breast cancer cells in a CL dose–dependent manner in vitro using CL photoactivation of DOX azide. Conclusion: We were able to develop a CL-activated “sticky tag” that converts the low CL signal into a stable and long-lasting, highly intense fluorescence signal. This fluorescent footprint of the radioactive signal might be clinically used for intraoperative surgery. The CL-targeted drug delivery strategy may potentially be used for dual-step targeted therapy. COPYRIGHT © 2018 by the Society of Nuclear Medicine and Molecular Imaging. |
| Keywords: | controlled study; unclassified drug; human cell; doxorubicin; drug safety; nonhuman; ultraviolet radiation; protein analysis; mouse; cell viability; image analysis; protein targeting; fluorescence; fluorescent dye; animal experiment; animal model; in vivo study; drug structure; drug synthesis; fibrosarcoma; luminescence; fluorodeoxyglucose f 18; radiopharmaceutical agent; photodynamics; signal processing; gallium 68; concentration response; fluorescence imaging; drug exposure; tissue specificity; vitronectin receptor; covalent bond; incubation time; azide; chemical labeling; cerenkov luminescence; human; female; priority journal; article; mda-mb-231 cell line; near-infrared optical imaging; photoactivatable; sticky tag; cy7 azide; cy7 dye; doxorubicin azide; tetraxetan arginylglycylaspartic acid y 90; fibrosarcoma cell; ht-1080 cell line |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 59 |
| Issue: | 1 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2018-01-01 |
| Start Page: | 58 |
| End Page: | 65 |
| Language: | English |
| DOI: | 10.2967/jnumed.117.198549 |
| PROVIDER: | scopus |
| PMCID: | PMC5750525 |
| PUBMED: | 28912146 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2018 -- Source: Scopus |
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