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Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study.

Ferrari C, Asabella AN, Villano C, Giacobbi B, Coccetti D, Panichelli P, Rubini G - Biomed Res Int (2015)

Bottom Line: To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy.Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact.Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells.

View Article: PubMed Central - PubMed

Affiliation: Nuclear Medicine, University "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy.

ABSTRACT
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [(64)Cu]CuCl2. To evaluate the potential theranostic role of [(64)Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [(64)Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

No MeSH data available.


Related in: MedlinePlus

Cell neurospheres, photographed at 40 magnification, after 1, 4, and 18 h of exposure to 64Cu radiation. The neurosphere-forming ability of GBM cell lines was progressively abolished.
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fig2: Cell neurospheres, photographed at 40 magnification, after 1, 4, and 18 h of exposure to 64Cu radiation. The neurosphere-forming ability of GBM cell lines was progressively abolished.

Mentions: A typical behavior of U-87MG cell lines is their tendency to coalesce in CSC medium to form globular structures called neurospheres (Figure 2). This activity could be viewed as a prerequisite for cancer cells to grow a tumor mass. It was observed that, after 18 h exposure to [64Cu]CuCl2, the neurosphere-forming ability of GBM cell lines was completely suppressed.


Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study.

Ferrari C, Asabella AN, Villano C, Giacobbi B, Coccetti D, Panichelli P, Rubini G - Biomed Res Int (2015)

Cell neurospheres, photographed at 40 magnification, after 1, 4, and 18 h of exposure to 64Cu radiation. The neurosphere-forming ability of GBM cell lines was progressively abolished.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663283&req=5

fig2: Cell neurospheres, photographed at 40 magnification, after 1, 4, and 18 h of exposure to 64Cu radiation. The neurosphere-forming ability of GBM cell lines was progressively abolished.
Mentions: A typical behavior of U-87MG cell lines is their tendency to coalesce in CSC medium to form globular structures called neurospheres (Figure 2). This activity could be viewed as a prerequisite for cancer cells to grow a tumor mass. It was observed that, after 18 h exposure to [64Cu]CuCl2, the neurosphere-forming ability of GBM cell lines was completely suppressed.

Bottom Line: To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy.Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact.Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells.

View Article: PubMed Central - PubMed

Affiliation: Nuclear Medicine, University "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy.

ABSTRACT
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a median survival time less than one year. To date, there are only a limited number of effective agents available for GBM therapy and this does not seem to add much survival advantage over the conventional approach based on surgery and radiotherapy. Therefore, the development of novel therapeutic approaches to GBM is essential and those based on radionuclide therapy could be of significant clinical impact. Experimental evidence has clearly demonstrated that cancer cells have a particularly high fractional content of copper inside the nucleus compared to normal cells. This behavior can be conveniently exploited both for diagnosis and for delivering therapeutic payloads (theranostic) of the radionuclide copper-64 into the nucleus of cancerous cells by intravenous administration of its simplest chemical form as dichloride salt [(64)Cu]CuCl2. To evaluate the potential theranostic role of [(64)Cu]CuCl2 in GBM, the present work reports results from a preclinical study carried out in a xenografted GBM tumor mouse model. Biodistribution data of this new agent were collected using a small-animal PET tomograph. Subsequently, groups of tumor implanted nude mice were treated with [(64)Cu]CuCl2 to simulate single- and multiple-dose therapy protocols, and results were analyzed to estimate therapeutic efficacy.

No MeSH data available.


Related in: MedlinePlus