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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 6/2010

01-12-2010 | Research Article

Radiochemical Synthesis, Rodent Biodistribution and Tumor Uptake, and Dosimetry Calculations of [11C] Methylated LY2181308

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

Published in: Molecular Imaging and Biology | Issue 6/2010

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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.
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Metadata
Title
Radiochemical Synthesis, Rodent Biodistribution and Tumor Uptake, and Dosimetry Calculations of [11C] Methylated LY2181308
Authors
Carmen S. Dence
Richard Laforest
Xiankai Sun
Terry L. Sharp
Michael J. Welch
Robert H. Mach
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 6/2010
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-010-0319-8

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