Magnetic nanoparticle biodistribution following intratumoral administration

Giustini, Andrew J.; Ivkov, Robert; Hoopes, P. Jack

doi:10.1088/0957-4484/22/34/345101

Cited by 90 publications

(76 citation statements)

References 18 publications

(31 reference statements)

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“…This is the reason why we referred to the MHT performed immediately (15 min) and one day after the injection of MNPs as "extracellular MHT" and "intracellular MHT", respectively. Giustini et al [18] used TEM to evaluate the time-dependent cellular uptake of intratumorally in- MNPs into the tumors [18]. Thus, our results ( Figure 3) are consistent with the findings reported by Giustini et al [18].…”

Section: Discussionsupporting

confidence: 91%

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

Kobayashi¹,

Ohki²,

Tanoue³

et al. 2017

OJAppS

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The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm 3 , the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 7 and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significant- ly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.

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Section: Discussionsupporting

confidence: 91%

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

Kobayashi¹,

Ohki²,

Tanoue³

et al. 2017

OJAppS

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“…Previous studies from our group suggest that mNP are largely extracellular at this time. 31 A qualitative, TEM-based, evaluation of tumors indicates that the majority of mNP are extracellular at the time of AMF initiation.…”

Section: Introductionmentioning

confidence: 99%

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model

Petryk

Giustini

Gottesman

et al. 2013

International Journal of Hyperthermia

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Purpose The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in mouse mammary adenocarcinoma model. Materials and Methods A thermal dose equivalent to 60 minutes at 43°C (CEM 60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumor (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch coated magnetic nanoparticles. Following mNP delivery, the mouse/tumor was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumor to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. Results Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p=0.09) when prescribed to the same thermal dose. Tumors treated with mNPH also demonstrated reduced peritumoral normal tissue damage. Conclusions Our results demonstrate similar tumor treatment efficacy when tumor heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumor hyperthermia. These results further indicate that this improvement is due to improved heat localization in the tumor.

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“…The uptake of nanoparticles across cell membranes is investigated using different tools such as cell culture, biodistribution studies, transmission electron microscopy (TEM) and fluorescence microscopy (Raut et al, 2010;Giustini et al, 2011;Kirthivasan et al, 2012). Preliminary investigations with dye-loaded nanoparticles highlight the uptake mechanisms of colloidal carriers (van Rooy et al, 2011).…”

Section: Original Articlementioning

confidence: 99%

In vivobrain microdialysis to evaluate FITC-dextran encapsulated immunopegylated nanoparticles

2012

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Magnetic nanoparticle biodistribution following intratumoral administration

Cited by 90 publications

References 18 publications

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model

In vivobrain microdialysis to evaluate FITC-dextran encapsulated immunopegylated nanoparticles

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