Protoporphyrin IX tracer fluorescence modulation for improved brain tumor cell lines visualization.

Piffaretti, Deborah; Burgio, Floriana; Thelen, Marcus; Kaelin-Lang, Alain; Paganetti, Paolo; Reinert, Michael; D'Angelo, Maria Luisa (2019). Protoporphyrin IX tracer fluorescence modulation for improved brain tumor cell lines visualization. Journal of photochemistry and photobiology. B, Biology, 201, p. 111640. Elsevier 10.1016/j.jphotobiol.2019.111640

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Fluorescence image guided surgical resection (FIGR) of high grade gliomas (HGGs) takes advantage of the accumulation of the tracer protoporphyrin IX (PpIX) in glioma cells following administration of 5-aminolevulinic acid (5-ALA). Occasionally, PpIX fluorescence intensity may be insufficient, thus compromising the efficacy and precision of the surgical intervention. The cause for the signal variation is unclear and strategies to improve the intensity of PpIX fluorescence are considered necessary. We have previously shown that differential expression of the epidermal growth factor receptor in glioblastoma cells affects PpIX fluorescence. Herein, we investigated other factors impairing PpIX accumulation and pharmacological treatments able to enhance PpIX fluorescence in glioblastoma cells displaying lower signal. In the present study we demonstrate that presence of serum in cell culture medium and differences in cellular confluence can negatively influence PpIX accumulation in U87 cell lines. We hypothesized that PpIX fluorescence intensity results from the interplay between the metabolic clearance of PpIX mediated by ferrochelatase and heme oxygenase-1 and the cellular efflux of PpIX through the ATP-binding cassette subfamily G member 2 (ABCG2). Based on the availability of compounds targeting these proteins and inhibiting them, in this study we used modulators such as genistein, an isoflavone able to inhibit ABCG2; deferoxamine, which chelate iron ions impairing FECH activity and tin protoporphyrin IX (SnPP), the specific HO-1 inhibitor. Finally, we showed the efficacy of a precisely tuned pharmacological treatment in increasing PpIX accumulation and consequently fluorescence in glioblastoma cells. This strategy may translate in more sensitive tracing of tumor cells in-vivo and improved FIGR of HGGs and possibly low grade gliomas (LGGs).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kaelin, Alain

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1873-2682

Publisher:

Elsevier

Language:

English

Submitter:

Andrea Stettler

Date Deposited:

19 Dec 2019 09:18

Last Modified:

04 Jan 2021 11:10

Publisher DOI:

10.1016/j.jphotobiol.2019.111640

Related URLs:

PubMed ID:

31734545

Uncontrolled Keywords:

5-aminolevulinic acid ABCG2 Ferrochelatase Heme oxygenase-1 Protoporphyrin IX

BORIS DOI:

10.7892/boris.137180

URI:

https://boris.unibe.ch/id/eprint/137180

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