Imaging brain tumor proliferative activity with [I-124]iododeoxyuridine

Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emissio n tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 M Bq (0.76-1.74 mCi) of [I-124]IUdR in 20 patients with brain tumors, includi ng meningiomas and gliomas, The PET images were directly compared with gado linium contrast-enhanced or T2-weighted magnetic resonance images. Estimate s for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct t he 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standar d uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also ca lculated from the 24-h image data. The Ki, SUV, and Tm/Br values were relat ed to tumor type and grade, tumor labeling index, and survival after the PE T scan, The plasma half-life of [I-124]IUdR was short (2-3 min), and the arterial p lasma input function was similar between patients (48 +/- 12 SUV*min). Plas ma clearance of the major radiolabeled metabolite ([I-124]iodide) varied so mewhat between patients and was markedly prolonged in one patient with rena l insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [I-124]iodide) remained in the tumors after the 24-h washout period, and this fraction var ied between the different tumor groups. Because the SUV and Tm:Br ratio val ues reflect both IUdR-DNA incorporated and exchangeable nonincorporated rad ioactivity, any residual nonincorporated radioactivity will amplify their v alues and distort their significance and interpretation. This was particula rly apparent in the meningioma and glioblastoma multiforme groups of tumors . Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2 .3 mu l/min/g (peak value for glioblastoma multiforme, GEM). Comparable SW and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and fro m 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. T hus, the range of values was much greater for Ki (similar to 8-fold) compar ed with that for SUV (similar to 2.2-fold) and Tm:Br (similar to 3-fold). T he expected relationships between Iii, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient sur vival) were observed. However, greater image specificity and significance o f the SUV and Tm:Br values would be obtained by achieving greater washout a nd clearance of the exchangeable fraction of residual (background) radioact ivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [I-124]IUdR administration.