# LABELED THYMIDINE:  DEVELOPMENT AS A PET IMAGING AGENT

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1993 · $109,010

## Abstract

The ultimate goal of our research is to develop an understanding of the
response of cancer and viral infections to therapy using measurements of
cellular DNA synthesis and positron emission tomography (PET) imaging.
In order to make meaningful measurements of cellular proliferation using
PET we are developing appropriate labeled nucleosides and producing
detailed biochemical and kinetic models of their metabolism.  Our ongoing
studies have developed the techniques needed to obtain PET images with
[C- 11] thymidine (TdR), which is incorporated in DNA and can be used to
monitor cellular proliferation.  We have already addressed a number of
the problems associated with interpreting the PET images of [C- 11]TdR
including the contributions to TdR metabolism of intracellular pools,
reutilization., and degradation.  To further validate imaging with
thymidine we are continuing to study the biochemistry and kinetics of TdR
metabolism.  In particular this proposal will study the distribution of
the major metabolite of thymidine, labeled CO2, and its tissue fixation.
This information is being combined into kinetic models.  We ire further
developing such models to simplify our data analysis scheme and to
produce images of DNA synthesis.  While thymidine is proving clinically
useful, we have begun to search for nucleoside analogs which will monitor
cell proliferation and have improved imaging characteristics.  We plan to
test the hypothesis that two diflourinated analogs of thymidine,
5-fluoro-l-(2'-fluoro-2'deoxy-beta-D-ribofuranosyl)uracil (FFUdR) and
5-fluoro-l-(2'-fluoro-2'-deoxy-beta-Darabinosyl)uracil (FFaraU), will
provide increased tumor to blood ratios and undergo little degradation in
vivo.  Such tracers when labeled with F-18 could greatly simplify imaging
of cell growth, by eliminating the need for analyzing metabolites.  As an
added benefit, these compounds are also taken up and retained in cells
infected by viruses.  We plan to test the hypotheses that these
nucleoside analogs, as well as the [F- 18] -labeled adenosine analog
(+/-)9-[(1beta,2alpha,3beta)-2,3-bis(hydroxymethyl)-l-cyclobutyl]adenine
(F-cyclobut-A), may be useful in detecting and following the response to
viral infections.  As a model we have chosen to study cytomegalovirus
(CMV) infection in mice, since CMV is a major problem in patients with
AIDS and those undergoing organ transplants.

## Key facts

- **NIH application ID:** 3178708
- **Project number:** 5R01CA039566-10
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** Anthony Frank Shields
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $109,010
- **Award type:** 5
- **Project period:** 1988-01-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178708

## Citation

> US National Institutes of Health, RePORTER application 3178708, LABELED THYMIDINE:  DEVELOPMENT AS A PET IMAGING AGENT (5R01CA039566-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178708. Licensed CC0.

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