Radiochemical synthesis, rodent biodistribution and tumor uptake, and dosimetry calculations of [11C] methylated LY2181308

Carmen S. Dence, Richard Laforest, Xiankai Sun, Terry L. Sharp, Michael J. Welch, Robert H. MacH

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: The aim of the study was to develop a rapid and reproducible method to label LY2181308, an antisense oligonucleotide to Survivin, with carbon-11 in order to study its in vivo biodistribution and tumor uptake in rodents and its human dosimetry based on baboon data. Methods: Randomly [ 11C] methylated LY2181308 was produced with [11C] methyl iodide. The biodistribution was performed in female Sprague-Dawley (SD) rats and EMT-6 tumor-bearing mice in the presence of nonradioactive LY2181308. Human dosimetry calculations were based on baboon PET studies. Results: In SD rats, the kidney and liver were the organs with the most accumulation of radioactivity. Tumor uptake in mice was also relatively high after 5 min and remained constant for up to 1 h. Baboon dosimetry suggested that up to 42 mCi of radioactivity could be administered to human with a dose-limiting organ being the kidneys with a radiation dose of 32 μGy/MBq (0.118 rad/mCi). Conclusions: [11C] Methylated LY2181308 to rodents and baboons showed its biodistribution, tumor uptake, and human dosimetry evaluation. These results should facilitate the understanding of the pharmacokinetics of LY2181308 prior to use as a potential new therapeutic agent in oncology as well as to warrant more in vivo validations as a potentially useful tumor-imaging agent.

Original languageEnglish (US)
Pages (from-to)608-615
Number of pages8
JournalMolecular Imaging and Biology
Volume12
Issue number6
DOIs
StatePublished - Dec 1 2010

Keywords

  • Carbon-11
  • Dosimetry
  • Oligonucleotides
  • PET
  • Tumor uptake

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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