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In fact, Abraxane nanoparticles rapidly dissociate in the bloodstream, generating albumin fragments>>17<<. Therefore, the 89Zr-NRep technology can be best applied for a variety of nanoparticle platforms whose tumour accumulation is mainly dictated by the enhanced permeability and retention effect.
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The phospholipid-chelator DSPE-DFO was prepared according to our previously described procedure>>24<<. Briefly, DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine) and 1-(4-Isothiocyana-tophenyl)-3-[6,17-dihyroxy-7,10,18,21-tetraoxo-27-[N-acetylhydro-xylamino)-6,11,17,22-tetraazaheptaeicosane]thiourea (DFO-p-NCS) were reacted in a 1:
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Liposomes were prepared using the sonication method, as previously reported>>24<<. Briefly, a lipid film was prepared by evaporating a chloroform solution containing the corresponding lipids in the desired proportion (Supplementary Table 1).
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an EBCO TR19/9 variable-beam energy cyclotron (Ebco Industries Inc., BC, Canada) via the 89Y(p,n)89Zr reaction and purified in accordance with previously reported methods to yield 89Zr with a specific activity of 195−497 MBq μg−1 (ref. >>25<<). Activity measurements were made using a Capintec CRC-15R Dose Calibrator (Capintec, Ramsey, NJ).
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A solution of 0.3 % DFO-bearing liposomes in PBS was reacted with 89Zr-oxalate at 40 °C for 2 h (ref. >>24<<). The labelled liposomes were separated from free unreacted 89Zr by spin filtration using 100 kDa molecular weight cutoff tubes (Millipore, Billerica, MA).
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The doxorubicin concentration was quantified as previously reported>>26<<. Briefly, immediately after gamma counting, tumour samples were homogenized in lysis buffer (10:
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Activity concentration was quantified at the end of the study by averaging the maximum values in at least 5 region of interests drawn on adjacent slices of tumour tissue>>27<<.
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The volume was calculated using the formula V=(LxS2)/2 (ref. >>28<<). Euthanasia was scheduled according to predetermined end points:
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Generally, the presented strategy has several advantages over the creation of so-called theranostic nanoparticles, which contain both a therapeutic and a diagnostic>>18<<. First, it enables accurate tumour accumulation imaging of (Food and Drug Administration (FDA) approved) nanoparticle drugs without the need for their chemical modification, guaranteeing the preservation of integrity, clinical grade and
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Furthermore, since PET imaging is a hot spot technique>>19<<, it does not require the acquisition of pre- and post-contrast images, followed by the analysis of changes in signal intensity, while this is required for both MRI and computed tomography (CT)20.
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since PET imaging is a hot spot technique19, it does not require the acquisition of pre- and post-contrast images, followed by the analysis of changes in signal intensity, while this is required for both MRI and computed tomography (CT)>>20<<. Not only is this time consuming but also very sensitive to inaccuracies as organ movement and image artifacts complicate the procedure.
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Although CT is an inherently quantitative imaging technique, it is severely hampered by poor detection sensitivity for exogenously administered agents, requiring unrealistically high dosages, effectively preventing translation>>20<<. MRI is significantly more sensitive than CT, but is still orders of magnitudes less sensitive than PET, necessitating the administration of high doses of iron oxide contrast agents. Currently, the only agent available is ferumoxytol,
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Currently, the only agent available is ferumoxytol, applied to treat iron-deficiency anaemia, and used off-label for MRI (ref. >>21<<). In light of a recent FDA warning (http:
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Since the technology does not necessitate modifying the clinical grade product and delineates a robust inclusion criterion, translation is within reach, which will help rejuvenate oncological nanotherapy>>23<<.
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