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

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.

• Authors: Carmen S Dence, Richard Laforest, Xiankai Sun, Terry L Sharp, Michael J Welch, Robert H Mach
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 12 Issue 6 Pg. 608-15 (Dec 2010) ISSN: 1860-2002 [Electronic] United States
• PMID: 20376567 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbon Radioisotopes
• LY 2181308
• Oligonucleotides
• Radiopharmaceuticals

Topics

• Adult
• Animals
• Carbon Radioisotopes (administration & dosage, pharmacokinetics)
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms (diagnostic imaging, metabolism)
• Oligonucleotides (administration & dosage, pharmacokinetics)
• Papio
• Radiation Dosage
• Radiometry (methods)
• Radionuclide Imaging
• Radiopharmaceuticals (administration & dosage, chemical synthesis, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Rodentia (metabolism)
• Tissue Distribution