A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT.
This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of (10)B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak (10)B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.
Cruickshank
G S
GS
University of Birmingham and University Hospital Birmingham, Birmingham, UK. garth.cruickshank@uhb.nhs.uk
Ngoga
D
D
Detta
A
A
Green
S
S
James
N D
ND
Wojnecki
C
C
Doran
J
J
Hardie
J
J
Chester
M
M
Graham
N
N
Ghani
Z
Z
Halbert
G
G
Elliot
M
M
Ford
S
S
Braithwaite
R
R
Sheehan
T M T
TM
Vickerman
J
J
Lockyer
N
N
Steinfeldt
H
H
Croswell
G
G
Chopra
A
A
Sugar
R
R
Boddy
A
A
D000368:Aged; D001812:Blood-Brain Barrier; D001896:Boron Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006113:United Kingdom
D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D008353:Mannitol; D010649:Phenylalanine; C033685:4-boronophenylalanine