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

We offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field. We show that under appropriately chosen conditions a therapeutic temperature rise is achievable in clinically relevant situations. We also show that in such cases it may paradoxically be harder to achieve the same therapeutic temperature rise in a preclinical model. We comment on the implications for the evidence-based translation of hyperthermia based interventions from the laboratory to the clinic.