Whole-Body Distribution and Brain Tumor Imaging with 11C-4DST: A Pilot Study

Recently, we developed [methyl-C-11]4'-thiothymidine (C-11-4DST) as an in vivo cell proliferation marker. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain tumor imaging of C-11-4DST in humans. Methods: Multiorgan biodistribution and radiation dosimetry of C-11-4DST were assessed in 3 healthy humans, who underwent 2-h whole-body PET scanning. Radiation dosimetry was estimated from the residence times of source organs using the OLINDA program. Six brain tumor patients underwent dynamic C-11-4DST scans with arterial blood sampling. These patients were also evaluated with C-11-methionine PET on the same day (n = 4) as, or 3 wk before (n = 2), C-11-4DST PET studies. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. Breakdown of the blood-brain barrier in tumor tissue was confirmed by gadolinium-enhanced T1-weighted MRI. Results: There were no serious adverse events in any subjects at any time during the study period. C-11-4DST PET demonstrated selective uptake in the bone marrow, which has a high rate of proliferation. In addition, high-level uptake was also seen in the liver. The highest absorbed organ dose was in the urinary bladder wall (17.6 mu Gy/MBq). The estimated effective dose for C-11-4DST was 4.2 mu Sv/MBq. C-11-4DST showed little uptake in normal brain tissues, resulting in low back-ground activity for imaging of brain tumors. In contrast, C-11-4DST PET demonstrated rapid uptake in aggressive tumor masses, whereas no signal of C-11-4DST was seen in clinically stable disease in which C-11-methionine uptake was high. The distribution pattern of C-11-methionine in tumor regions was not always identical to that of C-11-4DST. Analysis of plasma samples by high-performance liquid chromatography indicated that more than 60% of the radioactivity was present as unchanged C-11-4DST at 20 min. Conclusion: The initial findings of the present study in a small group of patients indicated that C-11-4DST PET is feasible for imaging of brain tumors. Dosimetry and pharmacologic safety were acceptable at the dose required for adequate PET images.