Optimizing retention of multimodal imaging nanostructures in sentinel lymph nodes by nanoscale size tailoring

Kjellman, Pontus; Zandt, René in ‘t; Fredriksson, Sarah; Strand, Sven‐Erik

doi:10.1016/j.nano.2014.01.007

Cited by 25 publications

(28 citation statements)

References 34 publications

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“…Here animal 2, injected with the medium concentration of NPs, had a slightly larger mean displacement than the high concentration animal 3. This indicates an intersubject variation in SPIO-NP uptake in the SLN and/or an uneven distribution of the NPs throughout the SLN, which has also previously been reported by Kjellman et al [7]. The varied mean magnetomotive displacement within the different cross sections in the same SLN similarly points to an uneven NP distribution within the SLN.…”

Section: Discussionsupporting

confidence: 82%

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

Evertsson

Cinthio

Kjellman³

et al. 2015

2015 IEEE International Ultrasonics Symposium (IUS)

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The drive to gain a better understanding of how diseases arise and how to provide ever-earlier detection are some of the key factors for the development of molecular imaging. Compared to other imaging modalities ultrasound has not received the same attention for molecular imaging mainly due to its limited contrast resolution, together with contrast agents confined to the intravascular space. To overcome these issues, new nano-sized contrast agents and new ultrasound imaging techniques e.g. photo acoustic imaging, have been developed. Another such imaging technique under development is magnetomotive ultrasound imaging (MMUS). We have previously developed a frequency and phase tracking algorithm which is able to detect superparamagnetic iron oxide nanoparticles (SPIO NPs) using MMUS, where our suggested first clinical application is to detect sentinel lymph nodes (SLNs) in breast cancer surgery. Recently we have shown detection of SPIO laden rat SLNs in situ.Here we present the feasibility of in vivo detection of SLNs in rats. The algorithm clearly pinpoints the NP laden SLN, even in presence of significant artefactual tissue movement. The magnetomotive displacement increased when a higher voltage was applied on the coil creating the magnetic field (e.g. 56.6% increasing the voltage from 20V to 50V). An uneven concentration distribution of NPs in the SLN was found. The maximum magnetomotive displacement difference between two different cross sections in one SLN was 9.76 times. The study also showed that for a higher concentration of NPs a lower magnetic coil excitation voltage could be used in order to create a magnetomotive displacement of a certain magnitude. The result from this in vivo study shows that the method has potential for future clinical use.

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Section: Discussionsupporting

confidence: 82%

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

Evertsson

Cinthio

Kjellman³

et al. 2015

2015 IEEE International Ultrasonics Symposium (IUS)

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“…[28][29][30] Tracers with particle sizes ranging from 4 to 1,000 nm were used in these studies. The purpose of these studies was to optimize tracer uptake in the SLNs to facilitate preoperative localization with MRI, rather than intraoperative detection.…”

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confidence: 99%

“…Kjellman et al 29 used monodisperse magnetic nanoparticles with a polyethylene glycol coating with sizes of 15 nm, 27 nm, and 57 nm. The 15 nm particles were observed to accumulate in the SLNs the fastest and in the highest concentrations.…”

mentioning

confidence: 99%

“…Although the coating is known to be a factor influencing in vivo nanoparticle distribution, particle size was demonstrated to be the most significant factor for interstitially administered tracers. 19,29,[32][33][34] The poor performance of the polyethylene glycol-coated 32 nm tracer compared to the other tracers is therefore likely explained by a combination of the particle size distribution and the coating. The observed differences between the dextran-coated tracers are most likely explained by the different particle size distributions of these tracers.…”

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confidence: 99%

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Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

Pouw¹,

Ahmed²,

Anninga³

et al. 2015

IJN

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Introduction Breast cancer staging with sentinel lymph node biopsy relies on the use of radioisotopes, which limits the availability of the procedure worldwide. The use of a magnetic nanoparticle tracer and a handheld magnetometer provides a radiation-free alternative, which was recently evaluated in two clinical trials. The hydrodynamic particle size of the used magnetic tracer differs substantially from the radioisotope tracer and could therefore benefit from optimization. The aim of this study was to assess the performance of three different-sized magnetic nanoparticle tracers for sentinel lymph node biopsy within an in vivo porcine model. Materials and methods Sentinel lymph node biopsy was performed within a validated porcine model using three magnetic nanoparticle tracers, approved for use in humans (ferumoxytol, with hydrodynamic diameter d H =32 nm; Sienna+ ® , d H =59 nm; and ferumoxide, d H =111 nm), and a handheld magnetometer. Magnetometer counts (transcutaneous and ex vivo), iron quantification (vibrating sample magnetometry), and histopathological assessments were performed on all ex vivo nodes. Results Transcutaneous “hotspots” were present in 12/12 cases within 30 minutes of injection for the 59 nm tracer, compared to 7/12 for the 32 nm tracer and 8/12 for the 111 nm tracer, at the same time point. Ex vivo magnetometer counts were significantly greater for the 59 nm tracer than for the other tracers. Significantly more nodes per basin were excised for the 32 nm tracer compared to other tracers, indicating poor retention of the 32 nm tracer. Using the 59 nm tracer resulted in a significantly higher iron accumulation compared to the 32 nm tracer. Conclusion The 59 nm tracer demonstrated rapid lymphatic uptake, retention in the first nodes reached, and accumulation in high concentration, making it the most suitable tracer for intraoperative sentinel lymph node localization.

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“…In order to improve these limitations, indocyanine green-incorporated polymer nanogels with a hydrodynamic diameter of approximately 30 nm, which is optimal for uptake by lymph nodes, have been developed. [19][20][21][22] In our previous reports, the formation of a nanocarrier with a core-shell structure was demonstrated through temperature-induced phase transitions in the melt state of a polyethylene glycol (PEG)/paclitaxel/Pluronic mixture. 23 Liquid PEG (molecular weight 400) was used as a paclitaxel solubilizer, and the polymer that encapsulated the paclitaxel was composed of Pluronic F-68.…”

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confidence: 99%

Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

Oh¹,

Yhee²,

Lee³

et al. 2014

IJN

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Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs) were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results clearly indicate that docetaxel-loaded Pluronic NPs could provide a strategy to achieve effective cancer therapy by simultaneous delivery to primary tumors, tumor lymphatics, and tumor-associated metastatic lymphatics.

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Optimizing retention of multimodal imaging nanostructures in sentinel lymph nodes by nanoscale size tailoring

Cited by 25 publications

References 34 publications

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model

Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

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Optimizing retention of multimodal imaging nanostructures in sentinel lymph nodes by nanoscale size tailoring

Cited by 25 publications

References 34 publications

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

In vivo magnetomotive ultrasound imaging of rat lymph nodes - a pilot study

Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in&nbsp;vivo porcine model

Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

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Comparison of three magnetic nanoparticle tracers for sentinel lymph node biopsy in an in vivo porcine model