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MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain

  • Clinical--patient studies
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Summary

Purpose

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 and materials

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.

Results and 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.

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Acknowledgements

This research has been supported by the National Cancer Institute (Cancer Therapy Evaluation Program, CA78170 and the supplement to UCLA Johnson Comprehensive Cancer Center Core Grant), the UCLA General Clinical Research Center and Pharmacyclics Inc. Image processing and analysis was performed in the Ahmanson-Lovelace Brain Mapping Center with the support of the following organizations and grants: Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Northstar Fund, and the National Center for Research Resources grants RR12169, RR13642 and RR08655.

Tom Lai, Andrew Frew, Anne Wagner and Jenaro Felix have provided technical assistance. Dale Miles from Pharmacyclics Inc. provided blood sample data for the participating patients.

Meeting presentations:

The blood brain barrier investigation was presented at the 45th American Society of Therapeutic Radiology and Oncology, October 2003, Salt Lake City, USA. The MGd tumor retention study was presented at the 9th annual meeting of Society of Neuro Oncology, November 2004, Toronto, Canada.

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Authors and Affiliations

  1. Inter-Departmental Graduate Program in Biomedical Physics, University of California at Los Angeles, Los Angeles, CA, USA

    Genevieve N. Wu, Judith M. Ford & Jeffry R. Alger

  2. Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA

    Judith M. Ford

  3. Department of Neurology and Ahmanson-Lovelace Brain Mapping Center, University of California at Los Angeles, Los Angeles, CA, USA

    Jeffry R. Alger

  4. Department of Radiological Sciences, University of California at Los Angeles, Los Angeles, CA, USA

    Jeffry R. Alger

  5. Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA

    Judith M. Ford & Jeffry R. Alger

  6. Inter-Departmental Graduate Program in Biomedical Physics, Ahmanson-Lovelace UCLA Brain Mapping Center, 660 Charles Young Drive South, Los Angeles, CA, USA

    Genevieve N. Wu

Authors
  1. Genevieve N. Wu
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Correspondence to Genevieve N. Wu.

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Wu, G.N., Ford, J.M. & Alger, J.R. MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain. J Neurooncol 77, 95–103 (2006). https://doi.org/10.1007/s11060-005-9101-1

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  • DOI: https://doi.org/10.1007/s11060-005-9101-1

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