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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

Whole-body mouse biodistribution images collected 1, 2, 4, and 20 hours after intravenous injection of 12 MBq of [64Cu]CuCl2. Increased tracer uptake is observed in the tumor graft (white arrow).
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fig1: Whole-body mouse biodistribution images collected 1, 2, 4, and 20 hours after intravenous injection of 12 MBq of [64Cu]CuCl2. Increased tracer uptake is observed in the tumor graft (white arrow).

Mentions: PET images collected 1, 2, 4, and 20 hours after injection showed a good visualization of tumor grafts in all animals (Figure 1). There was a prominent activity in tumors as compared to the opposite reference shoulder. As expected, whole-body images displayed a high liver uptake 1 hour after injection, followed by intestinal washout 20 hours after injection. No significant uptake was observed in the brain. The mean value of SUVmax (±SD) of GBM grafts was 3.6 ± 0.44 as compared to that in soft tissue (shoulder) that was 1.25 ± 0.14. The mean value of SUVmax in the liver was found to be as high as 20.3 ± 0.67 in 1-hour images and less than 9.8 ± 0.45 in late images. After normalization to liver uptake of SUVmax values in tumor, kidneys, and shoulder, the highest SUVmax was observed in GBM (11 ± 2.5%), which was remarkably higher than the reference shoulder (3.4 ± 0.5%) with statistically significant difference (p < 0.001).


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)

Whole-body mouse biodistribution images collected 1, 2, 4, and 20 hours after intravenous injection of 12 MBq of [64Cu]CuCl2. Increased tracer uptake is observed in the tumor graft (white arrow).
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Whole-body mouse biodistribution images collected 1, 2, 4, and 20 hours after intravenous injection of 12 MBq of [64Cu]CuCl2. Increased tracer uptake is observed in the tumor graft (white arrow).
Mentions: PET images collected 1, 2, 4, and 20 hours after injection showed a good visualization of tumor grafts in all animals (Figure 1). There was a prominent activity in tumors as compared to the opposite reference shoulder. As expected, whole-body images displayed a high liver uptake 1 hour after injection, followed by intestinal washout 20 hours after injection. No significant uptake was observed in the brain. The mean value of SUVmax (±SD) of GBM grafts was 3.6 ± 0.44 as compared to that in soft tissue (shoulder) that was 1.25 ± 0.14. The mean value of SUVmax in the liver was found to be as high as 20.3 ± 0.67 in 1-hour images and less than 9.8 ± 0.45 in late images. After normalization to liver uptake of SUVmax values in tumor, kidneys, and shoulder, the highest SUVmax was observed in GBM (11 ± 2.5%), which was remarkably higher than the reference shoulder (3.4 ± 0.5%) with statistically significant difference (p < 0.001).

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