Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe

Brito, Joseph; Golijanin, Borivoj; Kott, Ohad; Moshnikova, Anna; Mueller-Leonhard, Catrina; Gershman, Boris; Andreev, Oleg A.; Reshetnyak, Yana K.; Amin, Ali; Golijanin, Dragan

doi:10.1016/j.urology.2019.01.008

Cited by 15 publications

(12 citation statements)

References 30 publications

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“…In another imaging application, a fluorescent agent has been developed using ICG, an indocyanine near infrared (NIR) fluorescent dye widely used for circulatory imaging (Desmettre et al, 2000;Alander et al, 2012). ICG-pHLIP is expected to be given as a single intravenous injection for tumor targeting and identification of margins and micrometastasis in the vicinity of primary tumors to improve surgical resections (Golijanin et al, 2016;Brito et al, 2019). To target and visualize tumors, imaging will be performed 24 h after IV injection of ICG-pHLIP to ensure blood and tissue clearance of the agent that is not bound in tumors, optimizing the contrast for marking cancerous lesions.…”

Section: Targeting and Extracellular Delivery Of Cargo Moleculesmentioning

confidence: 99%

Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding

Reshetnyak

Moshnikova

Andreev

et al. 2020

Front. Bioeng. Biotechnol.

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The advantages of targeted therapy have motivated many efforts to find distinguishing features between the molecular cell surface landscapes of diseased and normal cells. Typically, the features have been proteins, lipids or carbohydrates, but other approaches are emerging. In this discussion, we examine the use of cell surface acidity as a feature that can be exploited by using pH-sensitive peptide folding to target agents to diseased cell surfaces or cytoplasms.

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Section: Targeting and Extracellular Delivery Of Cargo Moleculesmentioning

confidence: 99%

Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding

Reshetnyak

Moshnikova

Andreev

et al. 2020

Front. Bioeng. Biotechnol.

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“…With protocol modifications, in vivo applications are also possible. While high brightness and photostability of Alexa532 made it an appropriate fluorophore in feasibility studies, replacement it with a FDA‐approved dye such as ICG will yield similar results as shown by Brito et al [57] In addition, even though the intrinsically narrow field of view of confocal imaging currently prohibits its standalone application in intraoperative surgical guidance, combining it with an appropriate wide‐field modality may help to overcome this deficiency [17, 44, 58].…”

Section: Discussionmentioning

confidence: 99%

“…For clinical applications shorter labeling times are required. Brito et al were able to image urothelial carcinomas after irrigating tissue with fluorescent‐tagged pHLIP for a few minutes only [57]. Therefore, developing faster labeling protocols are feasible.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of dual‐contrast fluorescence imaging of pathological breast tissues

Mitrou

Feng

Khan

et al. 2021

Journal of Biophotonics

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The combination of intravital dye, methylene blue (MB), with molecular cancer marker, pH low insertion peptide (pHLIP) conjugated with fluorescent Alexa532 (Alexa532‐pHLIP), was evaluated for enhancing contrast of pathological breast tissue ex vivo. Fresh, thick breast specimens were stained sequentially with Alexa532‐pHLIP and aqueous MB and imaged using dual‐channel fluorescence microscopy. MB and Alexa532‐pHLIP accumulated in the nuclei and cytoplasm of cancer cells, respectively. MB also stained nuclei of normal cells. Some Alexa532‐pHLIP fluorescence emission was detected from connective tissue and benign cell membranes. Overall, Alexa532‐pHLIP showed high affinity to cancer, while MB highlighted tissue morphology. The results indicate that MB and Alexa532‐pHLIP provide complementary information and show promise for the detection of breast cancer.

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“…Brito et al. ( 26 ) performed NIR molecular imaging of isolated upper urinary tract specimens from 12 patients using an indocyanine green-coupled pHLIP (ICG-pHLIP), and pHLIP-mediated NIR molecular imaging detected more tumor lesions compared to ordinary white light examination (detection rate 78.9% vs. 100%). Golijanin et al.…”

Section: Discussionmentioning

confidence: 99%

Ex Vivo Near-Infrared Molecular Imaging of Human Upper Urinary Tract Urothelial Carcinoma With a CD47-Based Targeted Tracer

et al. 2022

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ObjectiveThe low detection rate of early and small tumors remains a clinical problem that urgently needs to be solved in the accurate diagnosis and treatment of upper urinary tract urothelial carcinoma (UTUC). The objective of this study is to evaluate the feasibility of CD47 as a target for optical molecular imaging of human UTUC and conduct preliminary ex vivo imaging experiments.MethodsWe firstly analyzed the genome-wide mRNA expression data from Gene Expression Omnibus (GEO). Paraffin-embedded tissue specimens comprising UTUC and normal urothelium were collected. All tissue specimens were used for immunohistochemistry to compare CD47 protein expression in normal and cancer tissue. Meanwhile, 12 patients undergoing radical nephroureterectomy were prospectively included in ex vivo imaging experiments. Freshly isolated upper urinary tract specimens were incubated with anti-CD47-Alexa Fluor 790 and then imaged under white light and near-infrared (NIR) light. Standard histopathologic evaluation was performed, and findings were correlated with CD47-targeted NIR molecular imaging.ResultsThe GEO data revealed that CD47 mRNA expression was higher in UTUC specimens than that in paracancer normal tissue. In immunohistochemical analysis, the CD47 protein expression level was higher in both non-muscle-invasive and muscle-invasive (stage ≥T2) UTUCs than that in normal uroepithelium, and the localization of CD47 protein was the tumor cell membrane. In the ex vivo imaging experiments, all patients were pathologically diagnosed with UTUC, and no adverse effects of anti-CD47-Alexa Fluor 790 on the histological structure of the tumor and normal uroepithelium were observed. In the NIR grayscale images, the mean fluorescence intensity of the tumor tissue was significantly higher than that of the adjacent normal background tissue, which greatly improved the visualization of the tumor.ConclusionsCD47-targeted NIR molecular imaging could be a feasible and powerful strategy for the accurate diagnosis of UTUC. Larger-scale randomized trials are needed.

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Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe

Cited by 15 publications

References 30 publications

Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding

Targeting Acidic Diseased Tissues by pH-Triggered Membrane-Associated Peptide Folding

Feasibility of dual‐contrast fluorescence imaging of pathological breast tissues

Ex Vivo Near-Infrared Molecular Imaging of Human Upper Urinary Tract Urothelial Carcinoma With a CD47-Based Targeted Tracer

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