title: Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O MRI: implications for boron neutron capture therapy of malignant brain tumours.
abstract: In addition to its common usage as a tracer in metabolic and physiological studies, deuterium possesses anti-tumoural activity and confers protection against gamma-irradiation. A more recent interest in deuterium emanates from the search for alternatives capable of improving neutron penetrance whilst reducing healthy tissue radiation dose deposition in boron neutron capture therapy of malignant brain tumours. Despite this potential clinical application, deuterium induces brain oedema, which is detrimental to neutron capture therapy. In this study, five adult male rats were titrated with deuterated drinking water while brain oedema was monitored via water proton magnetic resonance imaging. This report concludes that deuterium, as well as deuterium-induced brain oedema, possesses a uniform brain bio-distribution. At a steady-state blood fluid deuteration value of 16%, when the deuterium isotope fraction in drinking water was 25%, a mean oedematous volume change of 9 +/- 2% (p-value <0.001) was observed in the rat brain-this may account for neurological and behavioural abnormalities found in mammals drinking highly deuterated water. In addition to characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this report also estimates the impact of oedema on thermal neutron enhancement and effective dose reduction factors using simple linear transport calculations. While body fluid deuteration enhances thermal neutron flux penetrance and reduces dose deposition, oedema has the opposite effect because it increases the volume of interest, e.g., the brain volume. Thermal neutron enhancement and effective dose reduction factors could be reduced by as much as approximately 10% in the presence of a 9% water volume increase (oedema).
authors.affiliation: College of Physicians & Surgeons, Columbia University, New York, NY 10027, USA. dcm2104@columbia.edu
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Medina
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Charles S
authors.initials: CS
authors.lastname: Springer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016754:Boron Neutron Capture Therapy / Q000379:methods; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D001929:Brain Edema / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D003903:Deuterium / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014867:Water
chemical_list: D014867:Water; D003903:Deuterium