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A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript



Visual inspection and biopsy is the current standard of care for oral cancer diagnosis, but is subject to misinterpretation and consequently to misdiagnosis. Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based approach that may fulfill the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. Here, we present results from a phase I safety and feasibility study on fluorescent, topically applied PARPi-FL. Twelve patients with a histologically proven oral squamous cell carcinoma (OSCC) gargled a PARPi-FL solution for 60 s (15 mL, 100 nM, 250 nM, 500 nM, or 1000 nM), followed by gargling a clearing solution for 60 s. Fluorescence measurements of the lesion and surrounding oral mucosa were taken before PARPi-FL application, after PARPi-FL application, and after clearing. Blood pressure, oxygen levels, clinical chemistry, and CBC were obtained before and after tracer administration.


PARPi-FL was well-tolerated by all patients without any safety concerns. When analyzing the fluorescence signal, all malignant lesions showed a significant differential in contrast after administration of PARPi-FL, with the highest increase occurring at the highest dose level (1000 nM), where all patients had a tumor-to-margin fluorescence signal ratio of >3. A clearing step was essential to increase signal specificity, as it clears unbound PARPi-FL trapped in normal anatomical structures. PARPi-FL tumor cell specificity was confirmed by ex vivo tabletop confocal microscopy. We have demonstrated that the fluorescence signal arose from the nuclei of tumor cells, endorsing our macroscopic findings.


A PARPi-FL swish & spit solution is a rapid and non-invasive diagnostic tool that preferentially localizes fluorescent contrast to OSCC. This technique holds promise for the early detection of OSCC based on in vivo optical evaluation and targeted biopsy of suspicious lesions in the oral cavity.

Trial registration—NCT03085147, registered on March 21st, 2017.

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Squamous cell carcinoma of the oral cavity



PEG 300:

Polyethylene glycol 300


Regions of interest


Tumor to normal mucosal ratios




Lesion to margin ratio


Light-emitting diode


Memorial Sloan Kettering


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The authors gratefully acknowledge the support of the Memorial Sloan Kettering Cancer Radiochemistry & Molecular Imaging Probes Core, the Molecular Cytology Core, and the Memorial Sloan Kettering Center for Molecular Imaging & Nanotechnology. We especially thank Eric Chan for the help with the ImageJ plugins for PARP1 and PARPi-FL quantifications. We also thank Garon Scott for proofreading and Terry Helms for creating illustrations. We also thank the operating room nurses and the Head and Neck surgical faculty and clinical staff at MSK, especially Violeta Dokic, R.N. for the help with the patients.

Availability of data and materials

All data and material are made available.


This work was supported by National Institutes of Health grants P30 CA008748, R01 CA204441 (TR), and R43 CA228815 (CB and TR). Dr. Valero was sponsored by a grant from Fundación Alfonso Martín Escudero. The funding sources were not involved in study design, data collection and analysis, writing of the report, or the decision to submit this article for publication.

Author information

Authors and Affiliations



P.D.S.F., S.K., C.B; S.P., and T.R. conceived the study and designed the experiments. P.D.S.F, S.K., C.B, N.G., D.K.Z., D.A., C.V., R.G.G., H.S., I.G., S.P., and T.R. carried out the experiments and collected the data. C.B., S.R. and T.R. produced GMP PARPi-FL. P.D.S.F., C.B., R.A.G., S.P., and T.R. analyzed the data. P.D.S.F., S.K., C.B., N.G., W.A.W.; S.P., and T.R. wrote IRB protocols. P.D.S.F., C.B., A.M., S.P., and T.R. conducted statistical analysis of the data. P.D.S.F., S.K., C.B., and T.R. primarily wrote the manuscript.

Corresponding authors

Correspondence to Snehal G. Patel or Thomas Reiner.

Ethics declarations

Ethics approval

This study is compliant with the Health Insurance Portability and Accountability Act, was approved by the MSK Institutional Review Board, and was conducted per the Declaration of Helsinki ethical principles.

Consent for publication

All of the authors have read and approved the manuscript and possible conflict of interests are disclosed.

Conflict of interest

C.B., S.K., S.P., and T.R. are shareholders of Summit Biomedical Imaging, LLC. S.K., S.P., and T.R. are co-inventors on PCT application WO2016164771. T.R. is co-inventor on PCT application WO2012074840. T.R. is a paid consultant for Theragnostics, Inc. All the other authors have no relevant conflict to declare. This arrangement has been reviewed and approved by Memorial Sloan Kettering Cancer Center in accordance with its conflict of interest policies.

Key point question

Is the topical application of PARPi-FL safe? Can a mouthwash of the imaging agent provide a level of optical contrast (tumor to margin ratio) apparent to the human observer?

Pertinent findings

Topical application of PARPi-FL is safe and generated contrast-ratios above 3. A benign lesion did not take up the agent, and an undiagnosed contralateral small tumor was identified. PARPi-FL generates mesoscopic contrast by emitting a signal from its nuclear target on a subcellular level.

Implications for patient care

PARPi-FL is a simple, in vivo, non-invasive, cost-effective, molecularly specific, fluorescent contrast-based method to enhance oral cancer diagnosis.

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Demétrio de Souza França, P., Kossatz, S., Brand, C. et al. A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer. Eur J Nucl Med Mol Imaging 48, 3618–3630 (2021).

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