Dataset Information

Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent.

ABSTRACT: More sensitive and specific methods for early detection are imperative to improve survival rates in oral cancer. However, oral cancer detection is still largely based on visual examination and histopathology of biopsy material, offering no molecular selectivity or spatial resolution. Intuitively, the addition of optical contrast could improve oral cancer detection and delineation, but so far no molecularly targeted approach has been translated. Our fluorescently labeled small-molecule inhibitor PARPi-FL binds to the DNA repair enzyme poly(ADP-ribose)polymerase 1 (PARP1) and is a potential diagnostic aid for oral cancer delineation. Based on our preclinical work, a clinical phase I/II trial opened in March 2017 to evaluate PARPi-FL as a contrast agent for oral cancer imaging. In this commentary, we discuss why we chose PARP1 as a biomarker for tumor detection and which particular characteristics make PARPi-FL an excellent candidate to image PARP1 in optically guided applications. We also comment on the potential benefits of our molecularly targeted PARPi-FL-guided imaging approach in comparison to existing oral cancer screening adjuncts and mention the adaptability of PARPi-FL imaging to other environments and tumor types.

SUBMITTER: Kossatz S

PROVIDER: S-EPMC5582799 | biostudies-literature | 2017 Jan-Dec

REPOSITORIES: biostudies-literature

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Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent.

Kossatz Susanne S Weber Wolfgang W Reiner Thomas T

Molecular imaging 20170101

More sensitive and specific methods for early detection are imperative to improve survival rates in oral cancer. However, oral cancer detection is still largely based on visual examination and histopathology of biopsy material, offering no molecular selectivity or spatial resolution. Intuitively, the addition of optical contrast could improve oral cancer detection and delineation, but so far no molecularly targeted approach has been translated. Our fluorescently labeled small-molecule inhibitor ...[more]

PMID: 28856922

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Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy worldwide, and the precise detection is challenging currently. Magnetic particle imaging (MPI) is suitable for imaging deep and internal PDAC tumours because of its high sensitivity and unlimited imaging depth. The purpose of this study was to utilize the MPI, in combination with fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI), to advance the in vivo precise detection of PDAC xenografts.MethodsThe PDAC targeted plectin-1 peptide and IRDye800CW were conjugated to the superparamagnetic iron oxide nanoparticles (PTP-Fe3O4-IRDye800CW) for the PDAC-targeting triple-modality imaging. Subcutaneous and orthotopic PDAC mouse models were established. FMI, MPI, and MRI were performed for dynamic and quantitative observation of PDAC tumours. Histological staining analyses were used for ex vivo validation.FindingsPTP-Fe3O4-IRDye800CW nanoparticles possessed great triple-modality imaging performance and specific targeting to plectin-1 expressed on PDAC cells. For in vivo multi-modality imaging of orthotopic PDAC models, the PTP-Fe3O4-IRDye800CW nanoparticles demonstrated higher specificity, even distribution, and longer retention effects in tumours for over 7 d compared with Con-Fe3O4-IRDye800CW nanoparticles. (MPI, 2d post-injection: PTP-Fe3O4-IRDye800CW: 85.72% ± 1.53% vs. Con-Fe3O4-IRDye800CW: 74.41% ± 1.91%, **P < 0.01 (Student's t test)). Ex vivo histological and Prussian blue stainings were performed to validate the distribution of probes.InterpretationThese data demonstrate the feasibility of utilizing MPI for in vivo PDAC imaging and complement with FMI/MRI for a precise and comprehensive in vivo characterization of PDAC. This may benefit PDAC patients for precise diagnosis and guidance of therapy.FundingThis study was funded by the National Natural Science Foundation of China (Grant No. 62027901, 82071896, 81871422, 81871514, 81227901), Ministry of Science and Technology of China under Grant No. 2017YFA0205200, 2017YFA0700401, Beijing Natural Science Foundation (Grant No. 7212207), Elite Program of Dong Cheng District of Beijing (2020-dchrcpyzz-28), and Peking University Third Hospital (BYSYZD2019018, and jyzc2018-02).

Dataset Information

Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent.

Publications

Detection and Delineation of Oral Cancer With a PARP1-Targeted Optical Imaging Agent.

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