MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain.
OBJECTIVE
Motexafin gadolinium (MGd) is an investigational pharmaceutical with radiation enhancing properties. Magnetic Resonance Imaging (MRI) was used to measure brain and tumor MGd levels to evaluate (1) the degree to which MGd passes through the intact blood brain barrier, and (2) the retention of MGd in tumor in patients with glioblastoma multiforme (GBM).


METHODS
MRI studies were performed on GBM patients who participated in a phase I clinical trial in which MGd was given during standard fractionated radiation therapy. MGd was administered daily (Monday to Friday) for five or 10 doses as a loading regimen, followed by three times per week dosing as a maintenance schedule. T1-weighted MRI was performed at intervals throughout the course of the MGd administration and radiation therapy in the 33 participating patients. Eleven patients had pre- and post-MGd scans, allowing for study of MGd's normal blood brain barrier penetration. Twenty-two patients had adequate residual tumor for measurements to evaluate MGd retention in tumor during the course of MGd and radiation administration.


CONCLUSIONS
The studies of uninvolved brain tissue support the conclusion that MGd does not cross the intact blood brain barrier in detectable quantities. The tumor study showed MGd uptake during loading and maintenance without measurably significant fall off on non-dosage days during the maintenance dosing. Although the number of cases is small, the 10-day loading regimen showed greater drug loading and retention compared with the 5 days loading regimen.
Inter-Departmental Graduate Program in Biomedical Physics, University of California at Los Angeles, Los Angeles, CA, USA. nwu@ucla.edu
Genevieve N
GN
Wu
Judith M
JM
Ford
Jeffry R
JR
Alger
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D015331:Cohort Studies; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011879:Radiotherapy Dosage
D000970:Antineoplastic Agents; D008665:Metalloporphyrins; D011838:Radiation-Sensitizing Agents; C437683:motexafin gadolinium