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Development of (/sup 11/C)-. cap alpha. -aminoisobutyric acid and (/sup 18/F)-haloperidol as substrate-specific radiotracers

Thesis/Dissertation ·
OSTI ID:5212462

In light of the emergence of positron emission tomography (PET), two new substrate-specific radiotracers have been synthesized and evaluated as potential agents for the study of specific physiological processes: (1-/sup 11/C)-..cap alpha..-aminoisobutyric acid ((1-/sup 11/C)-AIB), a transport system-specific radiotracer for tumor localization and for the assessment of amino acid transport in vivo; and (/sup 18/F)-haloperidoll, a receptor-binding radiotracer for the assessment of brain dopamine receptors in vivo. AIB, a non-metabolized amino acid, accumulates in cells, particularly malignant cells, via the A type, or ''alanine-preferring'', amino acid transport system (1-/sup 11/C)-AIB in normal and in treated and untreated tumor-bearing rats, in tumor-bearing dogs, and in a tumor-bearing patient indicate rapid blood clearance and, concomitantly, rapid tissue localization, with slow net redistribution. Generally, there was selective localization in the kidney, in the liver, and in the pancreas, as well as in various tumors. The canine tumors and the human tumor were well visualized by external scintigraphy, especially when utilizing PET. (/sup 18/F)-Haloperidol, a dopamine receptor-binding neuroleptic of the butyrophenone series widely used in the management of schizophrenia was prepared via the Balz-Schiemann reaction. As the haloperdol dose administered to mice was increased from 0.01 to 1000 ..mu..g/kg, the relative concentration (..mu..Ci found per gm tisue sample/..mu..Ci injected per gm body mass) of (/sup 18/F)-haloperidol at 1 hr decreased from 30 to 1.0 in the striatum and from 8.0 to 1.0 in the cerebellum. The decrease in striatum radioactivity reflects competition between labeled and unlabeled haloperidol for dopamine receptors.

Research Organization:
Cornell Univ., New York (USA). Dept. of Medicine
OSTI ID:
5212462
Country of Publication:
United States
Language:
English

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