cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging

Yang, Xiaoqiang; Hong, Hao; Grailer, Jamison; Rowland, Ian J.; Javadi, Alireza; Hurley, Samuel A.; Xiao, Yuling; Yang, Yunan; Zhang, Yin; Nickles, Robert J.; Cai, Weibo; Steeber, Douglas A.; Gong, Shaoqin

doi:10.1016/j.biomaterials.2011.02.006

Cited by 403 publications

(258 citation statements)

References 39 publications

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“…Compared with the previous studies, our RGD-functionalized UCNPs showed relatively low uptake (;2.8 %ID/g at 4.5 h) in U87MG tumors. In another study, 124 I-labeled RGD-functionalized silica nanoparticles showed similarly low uptake (;2 %ID/g at 4 h) in tumors (29). The low uptake may be caused by deiodination of radioiodine from radioiodinated cyclic RGD.…”

Section: Discussionmentioning

confidence: 88%

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

et al. 2012

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Multimodal nanoparticles have been extensively studied for target-specific imaging and therapy of various diseases, including cancer. In this study, radiolabeled arginine-glycine-aspartic acid (RGD)-functionalized Er 31 /Yb 31 co-doped NaGdF 4 upconversion nanophosphors (UCNPs) were synthesized and evaluated as a multimodal PET/MR/optical probe with tumor angiogenesisspecific targeting properties. Methods: A dimeric cyclic RGDyk ((cRGDyk) 2 ) peptide was conjugated to polyacrylic acid-coated NaGdF 4 :Yb 31 /Er 31 UCNPs along with polyethylene glycol molecules and was consecutively radiolabeled with 124 I. In vitro cytotoxicity testing was performed for 3 d. Upconversion luminescence imaging of (cRGDyk) 2 -UCNP was performed on U87MG cells with a laboratory-made confocal microscope. In vivo small-animal PET and clinical 3-T T1-weighted MR imaging of 124 I-labeled RGD-functionalized UCNPs was acquired with or without blocking of cyclic RGD peptide in a U87MG tumor model. Inductively coupled plasma mass spectrometry and biologic transmission electron microscopy were done to evaluate gadolinium concentration and UCNP localization, respectively. Results: Polymer-coated UCNPs and dimeric RGD-conjugated UCNPs were monodispersely synthesized, and those of hydrodynamic size were 30 6 8 nm and 32 6 9 nm, respectively. (cRGDyk) 2 -UCNPs have a low cytotoxic effect on cells. Upconversion luminescence signals of (cRGDyk) 2 -UCNP were specifically localized on the surface of U87MG cells. 124 I-c(RGDyk) 2 -UCNPs specifically accumulated in U87MG tumors (2.8 6 0.8 vs. 1.3 6 0.4 percentage injected dose per gram in the blocking experiment), and T1-weighted MR images showed significant positive contrast enhancement in U87MG tumors. Tumor localization of 124 I-c(RGDyk) 2 -UCNPs was confirmed by inductively coupled plasma mass spectrometry and biologic transmission electron microscopy analysis. Conclusion: These results suggest that 124 Ilabeled RGD-functionalized UCNPs have high specificity for a v b 3 integrin-expressing U87MG tumor cells and xenografted tumor models. Multimodal UCNPs can be used as a platform nanoparticle with multimodal imaging for cancer-specific diagnoses.

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Section: Discussionmentioning

confidence: 88%

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

et al. 2012

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“…Although many interesting multimodal imaging probes have been suggested (34)(35)(36), their spatiotemporal characteristics have been investigated using each imaging device separately, making the exact correlation and comparison studies impossible. In contrast, our study with 64 Cu-NOTA-IO-MAN showed that high-sensitivity PET images for LN mapping were useful for confirming the accumulation of iron oxide nanoparticles in the same target region.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Yoon

Kim

et al. 2016

J Nucl Med

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Visualization of biologic processes at molecular and cellular levels has revolutionized the understanding and treatment of human diseases. However, no single biomedical imaging modality provides complete information, resulting in the emergence of multimodal approaches. Combining state-of-the-art PET and MRI technologies without loss of system performance and overall image quality can provide opportunities for new scientific and clinical innovations. Here, we present a multiparametric PET/MR imager based on a smallanimal dedicated, high-performance, silicon photomultiplier (SiPM) PET system and a 7-T MR scanner. Methods: A SiPM-based PET insert that has the peak sensitivity of 3.4% and center volumetric resolution of 1.92/0.53 mm 3 (filtered backprojection/ordered-subset expectation maximization) was developed. The SiPM PET insert was placed between the mouse body transceiver coil and gradient coil of a 7-T small-animal MRI scanner for simultaneous PET/MRI. Mutual interference between the MRI and SiPM PET systems was evaluated using various MR pulse sequences. A cylindric corn oil phantom was scanned to assess the effects of the SiPM PET on the MR image acquisition. To assess the influence of MRI on the PET imaging functions, several PET performance indicators including scintillation pulse shape, flood image quality, energy spectrum, counting rate, and phantom image quality were evaluated with and without the application of MR pulse sequences. Simultaneous mouse PET/MRI studies were also performed to demonstrate the potential and usefulness of the multiparametric PET/MRI in preclinical applications. Results: Excellent performance and stability of the PET system were demonstrated, and the PET/MRI combination did not result in significant image quality degradation of either modality. Finally, simultaneous PET/MRI studies in mice demonstrated the feasibility of the developed system for evaluating the biochemical and cellular changes in a brain tumor model and facilitating the development of new multimodal imaging probes. Conclusion: We developed a multiparametric imager with high physical performance and good system stability and demonstrated its feasibility for small-animal experiments, suggesting its usefulness for investigating in vivo molecular interactions of metabolites, and cross-validation studies of both PET and MRI.Key Words: PET/MRI; silicon photomultiplier (SiPM); hybrid imaging; multi-parametric imaging; dual-modality imaging probe Asubst antial role of small-animal imaging has been pinpointed in numerous studies in terms of understanding the underlying mechanism of human diseases and elucidating the efficacy of new therapeutic approaches. Among the in vivo small-animal imaging modalities, which are scaled down to dedicated devices from clinical ones, PET is the most-sensitive technique that is readily translatable to the clinic (1). Spatial and temporal distributions of compounds labeled with a positron-emitting radionuclide are noninvasively measured by the PET scanner. Consequently, the PET scanner p...

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“…The wider use of PET/MRI scanners will be greatly fostered by the use of agents that incorporate both PET isotopes and MRI contrast agents. Research work has been successful in developing combined probes, such as SPIOcoated PET tracers, that show great potential for use in cell tracking with PET/MRI [25,41,42].…”

Section: F-fdg Pet/ct With and Without Contrast In Liver Lesionsmentioning

confidence: 99%

Use of PET/MRI for identification and characterisation of liver lesions

Nasoodi

Syed

Afaq

et al. 2014

Clin Transl Imaging

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Magnetic resonance imaging (MRI) has long been considered the gold standard for evaluation of hepatic lesions. There has, however, been much recent interest in functional analysis of malignant lesions, and conventional imaging tests are no longer able to answer all the clinical questions. In the current era, anatomical characterisation, e.g. regarding size and density, is no longer deemed adequate. Combined imaging with PET/CT provides clarity and insight but at times can be challenging, especially in certain parts of the body such as the liver, pelvis and brain, where test sensitivity is compromised. PET/MRI, a hybrid imaging technology, can be used to improve upon the soft-tissue contrast offered by MRI and the biochemical and metabolic information provided by PET, with overall improvement in test sensitivity and hence increased diagnostic accuracy and improved tissue characterisation. Furthermore, various radiolabelled PET tracers can be used to improve the accuracy of staging, determination of the extent of disease, evaluation of treatment response, prognostic assessment and differentiation between post-therapeutic changes and tumour recurrence. In this article, we review the advantages of PET/MRI over conventional imaging in identifying and characterising liver lesions.

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cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging

Cited by 403 publications

References 39 publications

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Use of PET/MRI for identification and characterisation of liver lesions

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cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging

Cited by 403 publications

References 39 publications

RGD Peptide–Conjugated Multimodal NaGdF4:Yb3+/Er3+ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

RGD Peptide–Conjugated Multimodal NaGdF4:Yb3+/Er3+ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

Simultaneous Multiparametric PET/MRI with Silicon Photomultiplier PET and Ultra-High-Field MRI for Small-Animal Imaging

Use of PET/MRI for identification and characterisation of liver lesions

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RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis

RGD Peptide–Conjugated Multimodal NaGdF₄:Yb³⁺/Er³⁺ Nanophosphors for Upconversion Luminescence, MR, and PET Imaging of Tumor Angiogenesis