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Published on: June 14, 2018
Whole-body distribution and brain tumor imaging with (11)C-4DST: a pilot study
Jun Toyohara1, Tadashi Nariai, Muneyuki Sakata
1Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. toyohara@pet.tmig.or.jp
Unlabelled:
Recently, we developed [methyl-(11)C]4'-thiothymidine ((11)C-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 (11)C-4DST in humans.
Methods:
Multiorgan biodistribution and radiation dosimetry of (11)C-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 (11)C-4DST scans with arterial blood sampling. These patients were also evaluated with (11)C-methionine PET on the same day (n = 4) as, or 3 wk before (n = 2), (11)C-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. (11)C-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 μGy/MBq). The estimated effective dose for (11)C-4DST was 4.2 μSv/MBq. (11)C-4DST showed little uptake in normal brain tissues, resulting in low background activity for imaging of brain tumors. In contrast, (11)C-4DST PET demonstrated rapid uptake in aggressive tumor masses, whereas no signal of (11)C-4DST was seen in clinically stable disease in which (11)C-methionine uptake was high. The distribution pattern of (11)C-methionine in tumor regions was not always identical to that of (11)C-4DST. Analysis of plasma samples by high-performance liquid chromatography indicated that more than 60% of the radioactivity was present as unchanged (11)C-4DST at 20 min.
Conclusion:
The initial findings of the present study in a small group of patients indicated that (11)C-4DST PET is feasible for imaging of brain tumors. Dosimetry and pharmacologic safety were acceptable at the dose required for adequate PET images.
