# LABELED THYMIDINE--DEVELOPMENT AS A PET IMAGING AGENT

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 1987 · $36,055

## Abstract

Positron emission tomography (PET) offers the opportunity to measure tumor
metabolism in vivo.  PET utilizes quantitative measurements of
positron-labeled biochemical tracers, and kinetic models to measure
discrete metabolic processes in normal and pathologic tissues.
C-11-labeled thymidine (Tdr) is a potential imaging agent for PET, which we
plan to develop and test for the eventual purpose of quantitating tumor
growth.  Unlike other tracers used for PET (e.g. glucose, amino acids),
thymidine has a unique potential for quantitating DNA synthesis in vivo.
As a precursor in DNA synthesis, Tdr has found widespread use in the
quantitation of cell growth in vitro.  In contrast, its application to in
vivo measurements will require a more detailed knowledge of the
biochemistry and kinetics of its uptake.  For the most part, such
developmental studies are more readily conducted utilizing H-3 or C-11
labeled Tdr analyzed in tissue culture, excised tissues and isolated
organs.  Despite extensive study of Tdr metabolism over the years, key
problems still remain to be answered to properly interpret the measurement
of in vivo Tdr uptake.  These problems are:  1) To calculate DNA synthetic
rates, the relative utilization of endogenous and exogenous Tdr must be
known.  We plan to study this by using a Tdr analog, BudR, to measure the
contribution of exogenously introduced Tdr.  The importance of
reutilization of Tdr released by dying cells will also be studied, since
this will affect the size of exogenous pools.  2) The available kinetic
models of thymidine metabolism have not been tested for in vivo use.  In
order to further develop and validate these models we will obtain detailed
measurements of the time course of Tdr uptake and degradation in vivo.  3)
Previous comparisons between the measurement of labeled Tdr uptake in vivo
and more conventional measurements of cellular proliferation may not have
been done under optimal conditions, since no attempt was made to measure
DNA synthesis.  We plan to make such comparisons after we have gained
further understanding of the kinetics of Tdr metabolism.  The long range
goal of this work is to apply measurements of Tdr uptake with PET to
monitoring tumor growth and response to cytotoxic therapy in vivo.  To
achieve this goal, we plan to conduct these "pre-imaging" PET studies to
develop biochemical and kinetic models of Tdr metabolism which will be
necessary to convert the raw imaging data obtained with PET into
quantitative measurements of regional cellular proliferation.

## Key facts

- **NIH application ID:** 3178704
- **Project number:** 5R01CA039566-03
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **SAM.gov UEI:** HMSNCM57QNR5
- **Principal Investigator:** Anthony Frank Shields
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $36,055
- **Award type:** 5
- **Project period:** 1985-07-01 → 1987-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178704

## Citation

> US National Institutes of Health, RePORTER application 3178704, LABELED THYMIDINE--DEVELOPMENT AS A PET IMAGING AGENT (5R01CA039566-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178704. Licensed CC0.

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