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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

Representative PET image of MDG mouse number 6 showing 92% tumor volume reduction.
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fig3: Representative PET image of MDG mouse number 6 showing 92% tumor volume reduction.

Mentions: The tumor volume reduction from PET-1 to PET-2, expressed as percentage, for animals treated in SDG and MDG, is reported in Table 1. A good response to both single- and multiple-dose treatment was observed in almost all cases. In SDG, VOI reduction ranged from 68 to 94%, with complete tumor disappearance observed in two cases. In MDG, VOI reduction ranged from 64 to 92%, with complete tumor disappearance observed in four cases (Table 1, Figure 3).


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)

Representative PET image of MDG mouse number 6 showing 92% tumor volume reduction.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Representative PET image of MDG mouse number 6 showing 92% tumor volume reduction.
Mentions: The tumor volume reduction from PET-1 to PET-2, expressed as percentage, for animals treated in SDG and MDG, is reported in Table 1. A good response to both single- and multiple-dose treatment was observed in almost all cases. In SDG, VOI reduction ranged from 68 to 94%, with complete tumor disappearance observed in two cases. In MDG, VOI reduction ranged from 64 to 92%, with complete tumor disappearance observed in four cases (Table 1, Figure 3).

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