期刊
THERANOSTICS
卷 3, 期 3, 页码 181-189出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.5984
关键词
PET; fluorsence; dual modality; BODIPY; F-18-F-19 exchange
资金
- National Science Foundation [CHE-0952912]
- Welch Foundation [A-1423]
- USC Department of Radiology
- Department of Energy [DE-SC0002353]
- American Cancer Society [121991-MRSG-12-034-01-CCE]
- Robert E. and May R. Wright Foundation
- Southern California Clinical Translational Science Institute
- NNSF of Guangdong [U1032002]
- NNSF of China [81071206]
- National Cancer Institute [P30CA014089]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [0952912] Funding Source: National Science Foundation
Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [F-18]-fluoride into BODIPY dyes. Through a systematic optimization of the reaction conditions, we found that BODIPY dyes, including commercial amine-reactive BODIPY succinimidyl esters, may be converted into their radioactive analogues in the matter of minutes via a F-18-F-19 isotopic exchange reaction promoted by a Lewis acid such as SnCl4. An integrin-targeting RGD peptide was also conjugated with [F-18] BODIPY (R) R6G, derived from the commercially available BODIPY (R) R6G fluorescent tag, to provide a [F-18]-RGD conjugate in 82% yield. In vivo evaluation of this imaging probe showed a discernible tumor uptake in the U87MG xenograft model. The dual modality imaging properties of the probe was confirmed by ex vivo fluorescence and microPET imaging experiments. In summary, in the matter of minutes, BODIPY dyes were converted into their hot radioactive analogues via a F-18-F-19 isotopic exchange reaction promoted by a Lewis acid. This approach, which can be applied to commercial BODIPY dyes, provides easy access to positron emission tomography/fluorescence dual modality imaging agents.
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