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Biocompatible nanocomposite for PET/MRI hybrid imaging.

Locatelli E, Gil L, Israel LL, Passoni L, Naddaka M, Pucci A, Reese T, Gomez-Vallejo V, Milani P, Matteoli M, Llop J, Lellouche JP, Franchini MC - Int J Nanomedicine (2012)

Bottom Line: Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol.In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent (68)Ga incorporation.Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.

View Article: PubMed Central - PubMed

Affiliation: Department of Industrial Chemistry Toso Montanari. University of Bologna, Italy.

ABSTRACT
A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent (68)Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.

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TLC profiles obtained for 68Ga-labelled NPs (red line, Rf = 0) and free EDTA-68Ga complex (black line, Rf = 0.35).Note: The complex EDTA-68Ga is generated in situ.Abbreviations: TLC, thin layer chromatography; NPs, nanoparticles; EDTA, ethylenediaminetetra-acetic acid; NODA, 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid.
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f4-ijn-7-6021: TLC profiles obtained for 68Ga-labelled NPs (red line, Rf = 0) and free EDTA-68Ga complex (black line, Rf = 0.35).Note: The complex EDTA-68Ga is generated in situ.Abbreviations: TLC, thin layer chromatography; NPs, nanoparticles; EDTA, ethylenediaminetetra-acetic acid; NODA, 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid.

Mentions: A number of metallic PET isotopes have been used to date for NP labeling, including 64Cu,20 and 68Ga.21 Copper-64 has probably been the most widely used due to its relatively long half life (12.7 hours), which permits PET evaluation of slow biochemical pathways. However, the production of 64Cu requires the irradiation of 64Ni with protons, and a laborious purification process using anion exchange chromatography.22 Due to this fact 68Ga, which can be easily obtained from a commercially available 68Ge/68Ga generator, is gaining interest in the development of multimodal imaging agents, and its incorporation into NPs using bifunctional chelating agents has been already reported in the literature.23 In the current work, a similar procedure was followed but a preconcentration step was applied to the 68Ga3+ solution obtained from the generator.23 Under optimized experimental conditions (T = 60°C, t = 30 minutes, pH = 3.5), the labeling yield of Magh-1-PNPs-NODA, as measured by gamma-counting after filtration, was 84% ± 6%. Quality control of the NPs performed by TLC (Figure 4, red line) showed no peak corresponding to free 68Ga after filtration and reconstitution in physiologic saline. The stability of labeled NPs in physiologic saline solution and in rat serum was also determined by TLC. The fraction of free gallium at t = 90 minutes was <5% in both media (not shown in Figure 4). These results confirm the stability of the 68Ga-NODA complex, which is very appropriate for subsequent in vivo studies.


Biocompatible nanocomposite for PET/MRI hybrid imaging.

Locatelli E, Gil L, Israel LL, Passoni L, Naddaka M, Pucci A, Reese T, Gomez-Vallejo V, Milani P, Matteoli M, Llop J, Lellouche JP, Franchini MC - Int J Nanomedicine (2012)

TLC profiles obtained for 68Ga-labelled NPs (red line, Rf = 0) and free EDTA-68Ga complex (black line, Rf = 0.35).Note: The complex EDTA-68Ga is generated in situ.Abbreviations: TLC, thin layer chromatography; NPs, nanoparticles; EDTA, ethylenediaminetetra-acetic acid; NODA, 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526150&req=5

f4-ijn-7-6021: TLC profiles obtained for 68Ga-labelled NPs (red line, Rf = 0) and free EDTA-68Ga complex (black line, Rf = 0.35).Note: The complex EDTA-68Ga is generated in situ.Abbreviations: TLC, thin layer chromatography; NPs, nanoparticles; EDTA, ethylenediaminetetra-acetic acid; NODA, 2,2′-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid.
Mentions: A number of metallic PET isotopes have been used to date for NP labeling, including 64Cu,20 and 68Ga.21 Copper-64 has probably been the most widely used due to its relatively long half life (12.7 hours), which permits PET evaluation of slow biochemical pathways. However, the production of 64Cu requires the irradiation of 64Ni with protons, and a laborious purification process using anion exchange chromatography.22 Due to this fact 68Ga, which can be easily obtained from a commercially available 68Ge/68Ga generator, is gaining interest in the development of multimodal imaging agents, and its incorporation into NPs using bifunctional chelating agents has been already reported in the literature.23 In the current work, a similar procedure was followed but a preconcentration step was applied to the 68Ga3+ solution obtained from the generator.23 Under optimized experimental conditions (T = 60°C, t = 30 minutes, pH = 3.5), the labeling yield of Magh-1-PNPs-NODA, as measured by gamma-counting after filtration, was 84% ± 6%. Quality control of the NPs performed by TLC (Figure 4, red line) showed no peak corresponding to free 68Ga after filtration and reconstitution in physiologic saline. The stability of labeled NPs in physiologic saline solution and in rat serum was also determined by TLC. The fraction of free gallium at t = 90 minutes was <5% in both media (not shown in Figure 4). These results confirm the stability of the 68Ga-NODA complex, which is very appropriate for subsequent in vivo studies.

Bottom Line: Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol.In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent (68)Ga incorporation.Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.

View Article: PubMed Central - PubMed

Affiliation: Department of Industrial Chemistry Toso Montanari. University of Bologna, Italy.

ABSTRACT
A novel nanocarrier system was designed and developed with key components uniquely structured at the nanoscale for early cancer diagnosis and treatment. In order to perform magnetic resonance imaging, hydrophilic superparamagnetic maghemite nanoparticles (NPs) were synthesized and coated with a lipophilic organic ligand. Next, they were entrapped into polymeric NPs made of biodegradable poly(lactic-co-glycolic acid) linked to polyethylene glycol. In addition, resulting NPs have been conjugated on their surface with a 2,2'-(7-(4-((2-aminoethyl)amino)-1-carboxy-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid ligand for subsequent (68)Ga incorporation. A cell-based cytotoxicity assay has been employed to verify the in vitro cell viability of human pancreatic cancer cells exposed to this nanosystem. Finally, in vivo positron emission tomography-computerized tomography biodistribution studies in healthy animals were performed.

Show MeSH
Related in: MedlinePlus