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Essential developments in the reliable and effective use of heat in medicine include: 1) the ability to model energy
deposition and the resulting thermal distribution and tissue damage (Arrhenius models) over time in 3D, 2) the
development of non-invasive thermometry and imaging for tissue damage monitoring, and 3) the development of
clinically relevant algorithms for accurate prediction of the biological effect resulting from a delivered thermal dose in
mammalian cells, tissues, and organs. The accuracy and usefulness of this information varies with the type of thermal
treatment, sensitivity and accuracy of tissue assessment, and volume, shape, and heterogeneity of the tumor target and
normal tissue. That said, without the development of an algorithm that has allowed the comparison and prediction of the
effects of hyperthermia in a wide variety of tumor and normal tissues and settings (cumulative equivalent minutes/
CEM), hyperthermia would never have achieved clinical relevance. A new hyperthermia technology, magnetic
nanoparticle-based hyperthermia (mNPH), has distinct advantages over the previous techniques: the ability to target the
heat to individual cancer cells (with a nontoxic nanoparticle), and to excite the nanoparticles noninvasively with a noninjurious
magnetic field, thus sparing associated normal cells and greatly improving the therapeutic ratio. As such, this
modality has great potential as a primary and adjuvant cancer therapy. Although the targeted and safe nature of the
noninvasive external activation (hysteretic heating) are a tremendous asset, the large number of therapy based variables
and the lack of an accurate and useful method for predicting, assessing and quantifying mNP dose and treatment effect is
a major obstacle to moving the technology into routine clinical practice. Among other parameters, mNPH will require
the accurate determination of specific nanoparticle heating capability, the total nanoparticle content and biodistribution
in the target cells/tissue, and an effective and matching alternating magnetic field (AMF) for optimal and safe excitation
of the nanoparticles. Our initial studies have shown that appropriately delivered and targeted nanoparticles are capable of
achieving effective tumor cytotoxicity at measured thermal doses significantly less than the understood thermal dose
values necessary to achieve equivalent treatment effects using conventional heat delivery techniques. Therefore
conventional CEM based thermal dose - tissues effect relationships will not hold for mNPH. The goal of this effort is to
provide a platform for determining the biological and physical parameters that will be necessary for accurately planning
and performing safe and effective mNPH, creating a new, viable primary or adjuvant cancer therapy.
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