Modulation of organ uptake of 11C-labelled L-DOPA

doi:10.1016/S0969-8051(96)00149-7

Nuclear Medicine and Biology

Volume 24, Issue 1, January 1997, Pages 15-19

https://doi.org/10.1016/S0969-8051(96)00149-7 Get rights and content

Abstract

The present study was undertaken to investigate if pretreatment with pharmacological agents could change the organ uptake of ¹¹C-labelled l-DOPA, and especially if the urinary excretion could be decreased. l-[β-¹¹C]DOPA was injected IV into unanesthetized Sprague-Dawley rats. After 20 min the rats were decapitated and organs taken out for radioactivity measurements. The uptake in the organs was investigated in animals only given the tracer, and in animals pretreated with drugs such as decarboxylase inhibitors carbidopa and benserazide as well as the monoamine oxidase inhibitors deprenyl, clorgyline, and the COMT inhibitor OR-486. A marked decrease in the urinary radioactivity was observed after carbidopa and benserazide administration. HPLC analysis revealed that under native conditions the major part of urinary radioactivity existed as dopamine, which was eliminated by the decarboxylase inhibitors. After pretreatment with the COMT inhibitor OR-486, the radioactivity uptake in the pancreas increased fourfold as compared to non-treated animals. HPLC analysis showed that this correlated with a marked increase in radiolabelled DOPAC. In the other organs and with the other drugs, only small effects were observed. With l-[β-¹¹C]fluoroDOPA as a tracer, similar results were observed although the increase in the pancreas by OR-486 had a lower magnitude. These studies suggest that it might be possible to improve the diagnostic ratio of l-[β-¹¹C]DOPA or l-[¹⁸F]fluoroDOPA in whole-body PET studies by pretreating the patient with decarboxylase inhibitor for reducing the urinary excretion and potentially increase the target organ uptake by COMT inhibition.

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^☆: This work was in part supported by grants from the Swedish Cancer Society, and the Erik, Karin, and Gösta Selanders Foundation.

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Nuclear Medicine and Biology

Abstract

References (20)

Positron emission tomography in drug evaluation: Influence of three different catechol-O-methyltransferase inhibitors on metabolism of (NCA) 6-[¹⁸F]fluoro-l-dopa in rhesus monkey

Nucl. Med. Biol.

An automated liquid chromatographic plasma analysis of amino acids used in combination with positron emission tomography (PET) for determination of in vivo plasma kinetics

J. Pharm. Biomed. Anal.

Properties of novel effective and highly selective inhibitors of catechol-O-methyltransferase

Life Sci.

Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat

Eur. J. Pharmacol.

Effect of catechol-O-methyl transferase inhibition on peripheral and central metabolism of 6-[¹⁸F]fluoro-l-dopa

Eur. J. Pharmacol.

The APUD concept and hormone production

Clin. Endocrinol. Metab.

Pancreatic neuroendocrine tumors: Diagnosis with PET

Radiology

In vivo demonstration of enzyme activity in endocrine pancreatic tumors—decarboxylation of ¹¹C-DOPA to ¹¹C-dopamine

J. Nucl. Med.

Enzymatic synthesis of carboxy-¹¹C-labelled l-tyrosine, l-DOPA, l-tryptophan and 5-hydroxy-l-tryptophan

Acta Chem. Scand.

Enzymatic synthesis of some ¹¹C-labelled analogues of l-tyrosine and l-tryptophan

J. Label. Compd. Radiopharm.

Cited by (12)

<sup>11</sup>C-5-hydroxytryptophan positron emission tomography after radiofrequency ablation of neuroendocrine tumor liver metastases

Enzymatic synthesis of carbon-11 labeled methionine and its derivatives with immobilized γ-cyano-γ-aminobutyric acid synthase

In vitro and ex vivo autoradiographic studies of nicotinic acetylcholine receptors using [<sup>18</sup>F]fluoronorchloro- epibatidine in rodent and human brain

Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC-HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel

Biocatalysis in radiochemistry: Enzymatic incorporation of PET radionuclides into molecules of biomedical interest

6-[<sup>18</sup>F]fluoro-L-DOPA uptake in the rat pancreas is dependent on the tracer metabolism

Modulation of organ uptake of 11C-labelled L-DOPA☆

Abstract

Nucl. Med. Biol.

J. Pharm. Biomed. Anal.

Life Sci.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Clin. Endocrinol. Metab.

Pancreatic neuroendocrine tumors: Diagnosis with PET

Radiology

In vivo demonstration of enzyme activity in endocrine pancreatic tumors—decarboxylation of 11C-DOPA to 11C-dopamine

J. Nucl. Med.

Enzymatic synthesis of carboxy-11C-labelled l-tyrosine, l-DOPA, l-tryptophan and 5-hydroxy-l-tryptophan

Acta Chem. Scand.

Enzymatic synthesis of some 11C-labelled analogues of l-tyrosine and l-tryptophan

J. Label. Compd. Radiopharm.

Modulation of organ uptake of ¹¹C-labelled L-DOPA☆

In vivo demonstration of enzyme activity in endocrine pancreatic tumors—decarboxylation of ¹¹C-DOPA to ¹¹C-dopamine

Enzymatic synthesis of carboxy-¹¹C-labelled l-tyrosine, l-DOPA, l-tryptophan and 5-hydroxy-l-tryptophan

Enzymatic synthesis of some ¹¹C-labelled analogues of l-tyrosine and l-tryptophan