Dataset Information

Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor.

ABSTRACT: Recent emphasis has focused on the development of rationally designed polymer-based micelle carriers for drug delivery. The current work tests the hypothesis that target specificity can be enhanced by micelles with cancer-specific ligands. In particular, we describe the synthesis and characterization of a new gadolinium texaphyrin (Gd-Tx) complex encapsulated in an IVECT micellar system, stabilized through Fe(III) cross-linking and targeted with multiple copies of a specific ligand for the melanocortin 1 receptor (MC1R), which has been evaluated as a cell-surface marker for melanoma. On the basis of comparative MRI experiments, we have been able to demonstrate that these Gd-Tx micelles are able to target MC1R-expressing xenograft tumors in vitro and in vivo more effectively than various control systems, including untargeted or un-cross-linked Gd-Tx micelles. Taken in concert, the findings reported herein support the conclusion that appropriately designed micelles are able to deliver contrast agent payloads to tumors expressing the MC1R.

SUBMITTER: Barkey NM

PROVIDER: S-EPMC3807968 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor.

Barkey Natalie M NM Preihs Christian C Cornnell Heather H HH Martinez Gary G Carie Adam A Vagner Josef J Xu Liping L Lloyd Mark C MC Lynch Vincent M VM Hruby Victor J VJ Sessler Jonathan L JL Sill Kevin N KN Gillies Robert J RJ Morse David L DL

Journal of medicinal chemistry 20130809 16

Recent emphasis has focused on the development of rationally designed polymer-based micelle carriers for drug delivery. The current work tests the hypothesis that target specificity can be enhanced by micelles with cancer-specific ligands. In particular, we describe the synthesis and characterization of a new gadolinium texaphyrin (Gd-Tx) complex encapsulated in an IVECT micellar system, stabilized through Fe(III) cross-linking and targeted with multiple copies of a specific ligand for the melan ...[more]

PMID: 23863078

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Project description:BackgroundIron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.Methods and resultsIONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.ConclusionsThe presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

Project description:Background: Multiparametric magnetic resonance imaging (mpMRI) has emerged as a non-invasive modality to diagnose and monitor prostate cancer. Quantitative metrics on the regions of abnormality have shown to be useful descriptors to discriminate clinically significant cancers. In this study, we evaluate the reproducibility of quantitative imaging features using repeated mpMRI on the same patients. Methods: We retrospectively obtained the deidentified records of patients, who underwent two mpMRI scans within 2 weeks of the first baseline scan. The patient records were obtained as deidentified data (including imaging), obtained through the TCIA (The Cancer Imaging Archive) repository and analyzed in our institution with an institutional review board-approved Health Insurance Portability and Accountability Act-compliant retrospective study protocol. Indicated biopsied regions were used as a marker for our study radiologists to delineate the regions of interest. We extracted 307 quantitative features in each mpMRI modality [T2-weighted MR sequence image (T2w) and apparent diffusion coefficient (ADC) with b values of 0 and 1,400 mm/s2] across the two sequential scans. Concordance correlation coefficients (CCCs) were computed on the features extracted from sequential scans. Redundant features were removed by computing the coefficient of determination (R 2) among them and replaced with a feature that had the highest dynamic range within intercorrelated groups. Results: We have assessed the reproducibility of quantitative imaging features among sequential scans and found that habitat region characterization improves repeatability in ADC maps. There were 19 T2w features and two ADC features in radiologist drawn regions (native raw image), compared to 18 T2w and 15 ADC features in habitat regions (sphere), which were reproducible (CCC ?0.65) and non-redundant (R 2 ? 0.99). We also found that z-transformation of the images prior to feature extraction reduced the number of reproducible features with no detrimental effect. Conclusion: We have shown that there are quantitative imaging features that are reproducible across sequential prostate mpMRI acquisition at a preset level of filters. We also found that a habitat approach improves feature repeatability in ADC. A validated set of reproducible image features in mpMRI will allow us to develop clinically useful disease risk stratification, enabling the possibility of using imaging as a surrogate to invasive biopsies.

Dataset Information

Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor.

Publications

Development and in vivo quantitative magnetic resonance imaging of polymer micelles targeted to the melanocortin 1 receptor.

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