Uptake of labeled dianhydrogalactitol into human gliomas and nervous tissue

Area of Science:

• Pharmacokinetics and drug distribution studies.
• Neuro-oncology and brain tumor research.
• Radiopharmaceutical and tracer studies.

Background:

• Understanding drug delivery to the central nervous system (CNS) is crucial for treating brain tumors.
• 3H-dianhydrogalactitol (DAG) is an investigational agent with potential in cancer therapy.
• Limited data exists on the distribution of DAG in human brain tissues and tumors.

Purpose of the Study:

• To investigate the distribution and elimination of 3H-dianhydrogalactitol (DAG) in plasma, CSF, brain, and tumor tissues.
• To determine the extent of DAG penetration into the CSF and its half-life.
• To compare DAG accumulation in various brain tumor types versus intact white matter.

Main Methods:

• Intravenous administration of 3H-labeled DAG to 11 patients.
• Sampling of plasma, CSF, brain tissue, and tumor tissue.
• Radioactivity measurement to quantify DAG distribution and elimination.
• Analysis of unchanged DAG in CSF.

Main Results:

• DAG successfully entered the CSF and exhibited slow elimination with a half-life of approximately 20 hours.
• Unchanged DAG constituted 6%-30% of total radioactivity in the CSF.
• All studied tumors, except one meningioma, accumulated DAG more than intact white matter.
• The highest drug uptake was observed in benign astrocytic tumors.

Conclusions:

• DAG demonstrates penetration into the human CNS and sustained presence.
• Brain tumors, especially astrocytic types, show preferential accumulation of DAG compared to normal brain tissue.
• These findings support further investigation of DAG for brain tumor treatment, considering its distribution profile.