Nanoparticle Redistribution in PC3 Tumors Induced by Local Heating in Magnetic Nanoparticle Hyperthermia: In Vivo Experimental Study

Abstract

In magnetic nanoparticle hyperthermia, a required thermal dosage for tumor destruction greatly depends on nanoparticle distribution in tumors. The objective of this study is to conduct in vivo experiments to evaluate whether local heating using magnetic nanoparticle hyperthermia changes nanoparticle concentration distribution in prostatic cancer (PC3) tumors. In vivo animal experiments were performed on grafted PC3 tumors implanted in mice to investigate whether local heating via exposing the tumor to an alternating magnetic field (5 kA/m and 192 kHz) for 25 min resulted in nanoparticle spreading from the intratumoral injection site to tumor periphery. Nanoparticle redistribution due to local heating is evaluated via comparing microCT images of resected tumors after heating to those in the control group without heating. A previously determined calibration relationship between microCT Hounsfield unit (HU) values and local nanoparticle concentrations in the tumors was used to determine the distribution of volumetric heat generation rate (q‴MNH) when the nanoparticles were subject to the alternating magnetic field. sas,matlab, and excel were used to process the scanned data to determine the total heat generation rate and the nanoparticle distribution volumes in individual HU ranges. Compared to the tumors in the control group, nanoparticles in the tumors in the heating group occupied not only the vicinity of the injection site, but also tumor periphery. The nanoparticle distribution volume in the high q‴MNH range (>1.8 × 106 W/m3) is 10% smaller in the heating group, while in the low q‴MNH range of 0.6–1.8 × 106 W/m3, it is 95% larger in the heating group. Based on the calculated heat generation rate in individual HU ranges, the percentage in the HU range larger than 2000 decreases significantly from 46% in the control group to 32% in the heating group, while the percentages in the HU ranges of 500–1000 and 1000–1500 in the heating group are much higher than that in the control group. Heating PC3 tumors for 25 min resulted in significant nanoparticle migration from high concentration regions to low concentration regions in the tumors. The volumetric heat generation rate distribution based on nanoparticle distribution before or after local heating can be used in the future to guide simulation of nanoparticle redistribution and its induced temperature rise in PC3 tumors during magnetic nanoparticle hyperthermia, therefore, accurately predicting required thermal dosage for safe and effective thermal therapy.

Noninvasive intratumoral thermal dose determination during in vivo magnetic nanoparticle hyperthermia: combining surface temperature measurements and computer simulations

“…S2, the FMT images of the multifunctional nanocarriers 1 h before (at t ¼ 24 h) and 1 h after (t ¼ 25 h) MNH treatment, indicates that the nano-heaters distribution probably changed during the treatment. Similar MNH experimental results in a PC3 tumor model using microCT images were recently reported [74]. The result suggests that the nano-heaters might diffuse during MNH.…”

Mild Whole-Body Hyperthermia-Induced Interstitial Fluid Pressure Reduction and Enhanced Nanoparticle Delivery to PC3 Tumors: In Vivo Studies and Micro-Computed Tomography Analyses

“…PC3 xenograft tumors were implanted in 14 Balb/c Nu/Nu male mice (28-32 g, The Jackson Lab, Bar Harbor, ME), with one tumor in each mouse, similar to our previous experiments [19][20][21]. A PC3 cell solution containing 5*10 6 cells was injected into the left flank of the mouse using a 27-gauge needle (Tuberculin Syringe w/Needle by BD, Fischer Scientific, Springfield, NJ).…”

“…Recently, microCT imaging techniques have been proposed as a non-invasive and non-destructive method for investigating nanoparticle distribution in tumors. Although microCT does not allow direct visualization of individual nanoparticles, the accumulation of nanoparticles in tissue would result in a region with a much higher density than the rest of the tissue, thus, the density variations can be detected by a microCT system [19][20][21]. Several recent studies [19][20][21] have shown the feasibility of imaging and quantifying detailed 3-D nanoparticle distribution in both gels and tumors.…”

“…Although microCT does not allow direct visualization of individual nanoparticles, the accumulation of nanoparticles in tissue would result in a region with a much higher density than the rest of the tissue, thus, the density variations can be detected by a microCT system [19][20][21]. Several recent studies [19][20][21] have shown the feasibility of imaging and quantifying detailed 3-D nanoparticle distribution in both gels and tumors. From those microCT images, it is evident that the nanoparticles are mostly confined to the vicinity of the injection site after an intratumoral injection, and the nanoparticle distribution volume in the tumor can be calculated with high precision.…”

Magnetic hydrogel with long in situ retention time for self-regulating temperature hyperthermia

“…However, the small size of MNPs also boosts the risk of the in vivo redistribution, incurred by the release of dead cell intracellular solution and the enhancement of vascular permeability after hyperthermia once [1,2], spreading to the peripheral healthy tissue and lowering curative effect [3][4][5]. For instance, in the treatment of human prostate cancer on the mouse back, the 25 min hyperthermia resulted in the Fe 3 O 4 MNPs spreading from the intratumoral injection site to tumor periphery [2]. In the treatment of glioma in the rat thalamus, the dextran-coated Fe 3 O 4 MNPs were also found to spread into the surrounding tissue shortly after intratumoral injection [3].…”