# PET PROBES OF DOPAMINE NEURONS IN YOUNG AND AGED MACAQUE

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1992 · $147,967

## Abstract

DESCRIPTION (Investigator's Abstract):  Analogues of exogenous L-dopa will
be labeled with 18F and evaluated as PET probes of the dopaminergic
nigrostriatal nerve terminals in the brains of anesthetized rhesus
macaques.  Three tracers will be studied, 6-fluoro-L-dopa (6-FD),
6-fluoro-L-m-tyrosine (6-FMT), and
6-fluoro-beta-fluoromethylene-L-m-tyrosine (6-FMMT).  All are transported
into brain by the neutral amino acid carrier system and decarboxylated to
their respective amines.  The subsequent fates of the tracers are expected
to be sensitive to various striatal enzymes and mechanisms associated with
the storage, release, and metabolism of dopamine.  A total of 22 subjects
will be drawn from colonies at the Wisconsin Regional Primate Center.  Of
these, 4 will receive unilateral lesions of the nigrostriatal pathway by
infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).  The
other 18 will be drawn equally from two age groups:  10-15 years and
greater that 25 years.  Some studies in intact animals will be performed
following pharmacological manipulation of aspects of dopa and dopamine
transport and metabolism including inhibitions of amino acid transport,
decarboxylation, monoamine oxidases, and the storage of dopamine in
vesicles.  Dynamic PET imaging will be performed over a 4 hr period
following bolus administration of tracer; brain regions will be
established by correlation with MRI image data in the same subjects and
the regional time courses combined with measurements of plasma
concentrations of tracer and metabolites and analyzed by a variety of
mathematical data reduction and modeling tools.  The particular focus will
be to perform both model-independent and model-dependent characterization
the slowly-clearing, long-term kinetic components of the striatal time
courses of each tracer label, to establish their physiological and
neurochemical interpretation, and to investigate the stability of the loss
rates of such components in the face of aging and of neuron loss due to
lesioning.  The validated non-invasive tracer methods arising from this
project would be of critical importance in the study of early-stage
Parkinson's disease, and for the tracking of prospective neuroprotective
therapies.

## Key facts

- **NIH application ID:** 3122174
- **Project number:** 1R01AG010217-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** JAMES E HOLDEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $147,967
- **Award type:** 1
- **Project period:** 1992-06-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122174

## Citation

> US National Institutes of Health, RePORTER application 3122174, PET PROBES OF DOPAMINE NEURONS IN YOUNG AND AGED MACAQUE (1R01AG010217-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122174. Licensed CC0.

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