Dataset Information

Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging.

ABSTRACT: Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with (111)In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles.

SUBMITTER: Patil RR

PROVIDER: S-EPMC3182352 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging.

Patil Rajesh R RR Yu Jianhua J Banerjee Sangeeta R SR Ren Yong Y Leong Derek D Jiang Xuan X Pomper Martin M Tsui Benjamin B Kraitchman Dara L DL Mao Hai-Quan HQ

Molecular therapy : the journal of the American Society of Gene Therapy 20110712 9

Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanopar ...[more]

PMID: 21750533

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Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:BackgroundLead-212 (212Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (212Bi) via β-particle emission. This extends the problematic short half-life of 212Bi. In preparation for upcoming clinical trials with 212Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of 212Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation.ResultsBoth acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16-21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter.ConclusionsOnly minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of 212Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

Dataset Information

Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging.

Publications

Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging.

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