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

Paula Demétrio de Souza França, Susanne Kossatz, Christian Brand, Daniella Karassawa Zanoni, Sheryl Roberts, Navjot Guru, Dauren Adilbay, Audrey Mauguen, Cristina Valero Mayor, Wolfgang A. Weber, Heiko Schöder, Ronald A. Ghossein, Ian Ganly, Snehal G. Patel, Thomas Reiner

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

19 Zitate (Scopus)

Abstract

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.

OriginalspracheEnglisch
Seiten (von - bis)3618-3630
Seitenumfang13
FachzeitschriftEuropean Journal of Nuclear Medicine and Molecular Imaging
Jahrgang48
Ausgabenummer11
DOIs
PublikationsstatusVeröffentlicht - Okt. 2021

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