Radiopharmaceuticals for diagnosis and treatment. Progress report
In this grant period we have continued our efforts in the areas of PE basic radiochemistry, radiopharmaceutical synthesis, and preclinical radiopharmaceutical evaluation. A new synthetic sequence, consisting, of no-carrier-added fluorine-18 labeling of substituted benzaldehydes followed by reductive decarbonylation, has been developed. This new methodology can be applied to the fluorine-18 labeling of a wide variety of drugs not previously accessible through existing fluorine-18 labeling methods. Following up on a literature report that the ability to radiolabel aromatic rings can be predicted by {sup 13}C-NMR chemical shifts, we have examined the generality of this correlation in aromatic rings bearing a variety of substituents. Although the original correlation holds for nitro substituted anisaldehydes, it cannot be extended to other rings substitution patterns. We have examined the relationship of in vivo localization of various fluorine-18 labeled dopamine uptake inhibitors to their in vitro binding affinities and lipophilicities. We have found that remarkably small decreases in binding affinity result in dramatic losses of in vivo binding to the desired high affinity binding sites. In order to probe the effects of endogenous neurotransmitter on the in vivo binding of radiolabeled dopamine uptake inhibitors, we have examined the in vivo regional localization of [18{sub F}] GBR 13119 after acute and chronic drug treatments which alter the endogenous levels of dopamine. We have found that acute changes in dopamine levels do not affect the binding of this radioligand, but chronic depletion of neurotransmitter results in down-regulation of the in vivo binding sites. 16 refs., 2 figs., 1 tab.
- Research Organization:
- Michigan Univ., Ann Arbor, MI (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- FG02-88ER60639
- OSTI ID:
- 10106409
- Report Number(s):
- DOE/ER/60639--4; ON: DE92004065
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
CHEMICAL PREPARATION
DOPAMINE
FLUORINE 18
LABELLED COMPOUNDS
LIGANDS
NUCLEAR MEDICINE
POSITRON COMPUTED TOMOGRAPHY
PROGRESS REPORT
RADIOISOTOPE PRODUCTION
RADIOPHARMACEUTICALS
REACTION INTERMEDIATES
RECEPTORS
STRUCTURE-ACTIVITY RELATIONSHIPS
UNSEALED RADIONUCLIDES IN DIAGNOSTICS
UNSEALED RADIONUCLIDES IN THERAPY