Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway

J Nucl Med. 2017 Mar;58(3):374-378. doi: 10.2967/jnumed.116.182394. Epub 2016 Nov 3.

Abstract

18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors.

Keywords: PET; clofarabine; dosimetry.

MeSH terms

  • Absorption, Radiation / physiology
  • Adenine Nucleotides / pharmacokinetics*
  • Aged
  • Arabinonucleosides / pharmacokinetics*
  • Clofarabine
  • Deoxycytidine Kinase / metabolism*
  • Deoxyribonucleosides / metabolism*
  • Female
  • Fluorine Radioisotopes / pharmacokinetics*
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Molecular Imaging / methods
  • Organ Specificity / physiology
  • Positron-Emission Tomography / methods*
  • Radiation Dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Signal Transduction*
  • Tissue Distribution
  • Whole-Body Counting

Substances

  • Adenine Nucleotides
  • Arabinonucleosides
  • Deoxyribonucleosides
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Clofarabine
  • Deoxycytidine Kinase