Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles.

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Biomaterials. 2008 Oct 9.
Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles.van Landeghem FK, Maier-Hauff K, Jordan A, Hoffmann KT, Gneveckow U, Scholz R, Thiesen B, Brück W, von Deimling A.Institute of Neuropathology, Charité - Universitätsmedizin Berlin, CVK, 13353 Berlin, Germany.Patients
with glioblastoma multiforme (GBM), the most common primary brain tumor
in adults, have still a poor prognosis though new strategies of radio-
and chemotherapy have been developed. Recently, our group demonstrated
the feasibility, tolerability and anti-tumoral effects of a newly
developed therapeutic approach, termed thermotherapy using magnetic
nanoparticles or magnetic fluid hyperthermia (MFH), in a murine model
of malignant glioma. Currently, the efficacy of MFH is being evaluated
in a phase II study. Here, we report on post-mortem neuropathological
findings of patients with GBM receiving MFH. In brain autopsies the
installed magnetic nanoparticles were dispersed or distributed as
aggregates within geographic tumor necroses, restricted in distribution
to the sites of instillation. Therefore, our results underscore the
need for multiple trajectories of instillation. The typical GBM
necrosis with pseudopalisading was free of particles. Dispersed
particles and particle aggregates were phagocytosed mainly by
macrophages whereas glioblastoma cells showed an uptake to a minor
extent. MFH therapy further promotes uptake of nanoparticles in
macrophages, likely as a consequence of tumor inherent and therapy
induced formation of necrosis with subsequent infiltration and
activation of phagocytes. We did not observe bystander effects of MFH
such as sarcomatous tumour formation, formation of a sterile abscess or
foreign body giant cell reaction. Furthermore, all patients did not
present any clinical symptoms related to possible adverse effects of