Optical Imaging Modalities: Principles and Applications in Preclinical Research and Clinical Settings

Pirovano, Giacomo; Roberts, Sheryl; Kossatz, Susanne; Reiner, Thomas

doi:10.2967/jnumed.119.238279

Cited by 61 publications

(53 citation statements)

References 92 publications

(95 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Fluorescence-guided imaging using molecularly targeted agents to delineate tumors for diagnosis and to guide surgical resection has started to enter the clinical research space in recent years (30). These include studies on ovarian, colorectal and breast cancer (31). While only late stage clinical studies will be able to prove the added clinical value in terms of survival benefit of these newer modalities compared to standard diagnosis and surgical resection, early phase clinical studies are crucial to show feasibility of lesion detection, dose-finding, and provide exploratory data on sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

A Phase I Study of a PARP1-targeted Topical Fluorophore for the Detection of Oral Cancer

França

Kossatz

Zanoni

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

PurposeVisual 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 fulfil 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.Patients and MethodsTwelve patients with a histologically proven squamous cell carcinoma of the oral cavity (OSCC) gargled a PARPi-FL solution for 60 seconds (15 mL, 100 nM, 250 nM, 500 nM, or 1000 nM), followed by gargling a clearing solution for 60 seconds. 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.ResultsPARPi-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.ConclusionsA 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.Translational RelevanceDespite their accessible location, oral cavity cancers are often diagnosed late, especially in low-resource areas where their incidence is typically high. The high prevalence of premalignant and benign oral lesions in these populations contributes to a number of issues that make early detection of oral cancer difficult: even in experienced hands, it can be difficult to differentiate cancer from premalignant or benign lesions during routine clinical examination; and biopsy-based histopathology, the current standard of care, is invasive, prone to sampling error, and requires geographic access to appropriate health care professionals, including a highly trained pathologist. While seemingly impenetrable economic and infrastructure barriers have confounded the early diagnosis of oral cancer for most of the world’s population, these could be circumvented by a simple, in vivo, non-invasive, cost-effective, point-of-care method of diagnosis. We are attempting to address this unmet clinical need by using topically applied PARPi-FL — a molecularly specific, fluorescent contrast-based approach — to detect oral cancer.FundingThis 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.Disclosure of Potential Conflicts of InterestC.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.

show abstract

Section: Discussionmentioning

confidence: 99%

A Phase I Study of a PARP1-targeted Topical Fluorophore for the Detection of Oral Cancer

França

Kossatz

Zanoni

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…reduced nicotinamide adenine dinucleotide (NADH), hemoglobin or collagen), or reporter genes (e.g. Green Fluorescent Protein) [152,153]. This technology includes modalities such as Fluorescence Imaging, Bioluminescent Imaging, Optical Coherence Tomography (OCT), Photoacoustic Imaging, Diffuse Optical Tomography (DOT), Super-resolution Microscopy and Terahertz Tomography [152,154,155].…”

Section: Optical Imagingmentioning

confidence: 99%

“…Optical imaging has the potential to be noninvasive, nontoxic and cost-effective to quantify vascularization, permeability, hemoglobin, oxygen saturation (StO2) and concentration in breast tumors. Studies have shown that vascularization and StO2 of breast tumors are related to hypoxia, which is highly associated with malignant tumors due to their size [151,153].…”

Section: Optical Imagingmentioning

confidence: 99%

See 1 more Smart Citation

Breast cancer, screening and diagnostic tools: All you need to know

Barba

León-Sosa

Lugo

et al. 2021

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

show abstract

“…MI is used to study conditions that underlie normal physiology and pathologies. MI modalities include, but are not limited to, fluorescence imaging, bioluminescence imaging, near-infrared imaging (NIR), single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging [12][13][14][15]. While the sensitivity of these modalities varies, they can provide information of high spatiotemporal resolution.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors

Lau¹,

Rousseau²,

Kwon³

et al. 2020

Pharmaceuticals

View full text Add to dashboard Cite

Kinins, bradykinin and kallidin are vasoactive peptides that signal through the bradykinin B1 and B2 receptors (B1R and B2R). B2R is constitutively expressed in healthy tissues and mediates responses such as vasodilation, fluid balance and retention, smooth muscle contraction, and algesia, while B1R is absent in normal tissues and is induced by tissue trauma or inflammation. B2R is activated by kinins, while B1R is activated by kinins that lack the C-terminal arginine residue. Perturbations of the kinin system have been implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. In general, excess activation and signaling of the kinin system lead to a pro-inflammatory state. Depending on the disease context, agonism or antagonism of the bradykinin receptors have been considered as therapeutic options. In this review, we summarize molecular imaging agents targeting these G protein-coupled receptors, including optical and radioactive probes that have been used to interrogate B1R/B2R expression at the cellular and anatomical levels, respectively. Several of these preclinical agents, described herein, have the potential to guide therapeutic interventions for these receptors.

show abstract

Optical Imaging Modalities: Principles and Applications in Preclinical Research and Clinical Settings

Cited by 61 publications

References 92 publications

A Phase I Study of a PARP1-targeted Topical Fluorophore for the Detection of Oral Cancer

A Phase I Study of a PARP1-targeted Topical Fluorophore for the Detection of Oral Cancer

Breast cancer, screening and diagnostic tools: All you need to know

A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors

Contact Info

Product

Resources

About