Identification of infusion strategy for achieving repeatable nanoparticle distribution and quantification of thermal dosage using micro-CT Hounsfield unit in magnetic nanoparticle hyperthermia

Abstract

An infusion rate of 3 µL/min was identified to result in the most repeatable nanoparticle distribution in PC3 tumours. Linear relationships have been obtained to first convert micro-CT greyscale values to HU values, then to local nanoparticle concentrations, and finally to nanoparticle-induced q(MNH) values. The total energy deposition rate in tumours was calculated and the observed similarity in total energy deposition rates in all three infusion rate groups suggests improvement in minimising nanoparticle leakage from the tumours. The results of this study demonstrate that micro-CT generated q(MNH) distribution and tumour physical models improve predicting capability of heat transfer simulation for designing reliable treatment protocols using magnetic nanoparticle hyperthermia.

Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models

“…a tumour) is itself heterogeneous, and in any case, the interstitial administration of any fluid will naturally result in a higher concentration of material near the tip of the needle than at a distance further removed from the tip. That said, there are strategies (discussed in more detail in Section "In vitro, preclinical and clinical measurements of V d /V i ") that can be adopted to abrogate these effects, including the use of slow infusion rates [17][18][19][20][21] and reflux-resistant catheters [20,22], and performing multiple-site small-volume injections rather than a single large-volume injection [2,3,10,23]. Theoretical models of the diffusion mehanistics can also be called upon to help understand the process and design best-practice administration protocols [23,24].…”

“…For this reason, CT imaging is the preferred modality. This applies both to clinical CT studies, such as those undertaken by the MagForce team as part of their patient-specific treatment planning [10,[28][29][30], and also to preclinical micro-focussed CT studies [18,[31][32][33].…”

“…In vitro, preclinical and clinical measurements of V d /V i Consequently, despite the complexity of the inter-related physical, chemical and material factors that contribute to V d /V i for a given system, progress has been made towards understanding and, just as importantly, controlling the interstitial administration process. For example, Zhu et al have conducted some illuminating studies on infusion strategies for magnetic fluids, using both in vitro gel phantoms [17], and in vivo murine models [18]. They reported that quasihomogeneous in vivo dispersions (as measured by micro-CT) could be repeatably obtained using a syringe pump to provide very slow (3 ll/min for 30 min) intratumoural delivery of the agent through a very fine gauge (26 gauge, 0.26 mm inner diameter) needle [18].…”

“…For example, Zhu et al have conducted some illuminating studies on infusion strategies for magnetic fluids, using both in vitro gel phantoms [17], and in vivo murine models [18]. They reported that quasihomogeneous in vivo dispersions (as measured by micro-CT) could be repeatably obtained using a syringe pump to provide very slow (3 ll/min for 30 min) intratumoural delivery of the agent through a very fine gauge (26 gauge, 0.26 mm inner diameter) needle [18]. Furthermore, they were able to systematically vary the V d /V i dispersion factor in xenograft tumours from 0.77 ± 0.06 at the 3 ll/min rate, up to 1.26 ± 0.24 at a faster 5 ll/min rate [18].…”

“…The largest doses we found were ca. 25 mg Fe per mouse, as used by the Zhu group [18,31]. At a glance these seem high doses, although it should be noted that they were achieved using that group's controlled infusion strategy, so that near 100% interstitial retention might be assumed.…”