A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer.
Background: 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 si...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 48; no. 11; pp. 3618 - 3631 |
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| Autores principales: | , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Oct2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=152447042&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 152447042 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Oct2021 vid: 48 iid: 11 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 152447042 150139807 10.1007/s00259-021-05372-6 152447042 ppf: 3618 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer. aug: au: Demétrio de Souza França, Paula Kossatz, Susanne Brand, Christian Karassawa Zanoni, Daniella Roberts, Sheryl Guru, Navjot Adilbay, Dauren Mauguen, Audrey Valero Mayor, Cristina Weber, Wolfgang A. Schöder, Heiko Ghossein, Ronald A. Ganly, Ian Patel, Snehal G. Reiner, Thomas affil: Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, 10065, New York, NY, USA sug: ab: Background: 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. Results: 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. Conclusions: 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: Clinicaltrials.gov—NCT03085147, registered on March 21st, 2017. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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