Imaging brain tumor proliferative activity with [124I]iododeoxyuridine

Area of Science:

• Nuclear Medicine
• Oncology
• Radiochemistry

Background:

• Assessing brain tumor proliferation is crucial for treatment planning and prognosis.
• Positron emission tomography (PET) using radiotracers like iododeoxyuridine ([124I]IUdR) offers a non-invasive method for imaging tumor cellularity.
• Standard uptake values (SUVs) and tumor-to-brain ratios (Tm:Br) are commonly used PET metrics, but their accuracy can be influenced by non-incorporated radioactivity.

Purpose of the Study:

• To evaluate the accuracy of [124I]IUdR PET imaging in quantifying brain tumor proliferation.
• To compare the reliability of standard uptake values (SUVs) and tumor-to-brain ratios (Tm:Br) with pharmacokinetic modeling for estimating iododeoxyuridine-DNA incorporation (Ki).
• To investigate the impact of residual non-incorporated radioactivity on PET metrics and its relationship with tumor characteristics and patient survival.

Main Methods:

• 20 patients with brain tumors underwent [124I]IUdR PET imaging at 0-48 minutes and 24 hours post-injection.
• PET images were compared with MRI findings.
• Pharmacokinetic modeling was used to estimate Ki by analyzing dynamic PET data and correcting for residual radioactivity at 24 hours.
• SUVs and Tm:Br were calculated from 24-hour PET data.

Main Results:

• The plasma half-life of [124I]IUdR was short (2-3 min), but residual non-incorporated radioactivity ([124I]iodide) remained in tumors (15-93%) after 24 hours, varying by tumor type.
• Residual radioactivity significantly amplified SUV and Tm:Br values, particularly in meningiomas and glioblastomas.
• Ki values showed a wider range (8-fold) compared to SUV (2.2-fold) and Tm:Br (3-fold), demonstrating greater sensitivity to proliferation differences.
• Ki, SUV, and Tm:Br correlated with tumor type, grade, labeling index, and patient survival, but Ki provided more specific information.

Conclusions:

• Pharmacokinetic modeling to determine Ki offers a more accurate assessment of [124I]IUdR-DNA incorporation in brain tumors compared to SUVs and Tm:Br.
• Residual non-incorporated radioactivity in tumors can distort SUV and Tm:Br values, limiting their diagnostic significance.
• Optimizing tracer clearance through hydration or later imaging times may enhance the specificity of SUV and Tm:Br measurements.