title: Whole-body distribution and brain tumor imaging with (11)C-4DST: a pilot study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. toyohara@pet.tmig.or.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Toyohara
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nariai
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Sakata
authors.forename: Keiichi
authors.initials: K
authors.lastname: Oda
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawabe
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kubota
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology*; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D049109:Cell Proliferation; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011874:Radiometry / Q000379:methods; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000473:pathology; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D002250:Carbon Radioisotopes