Synthesis, Label and Biodistribution of 18F-Fethypride for Dopamine Receptor Imaging†

doi:10.7503/cjcu20131061

Abstract

Abstract:

Dopamine is one of important neurotransmitters in the brain, many diseases of the nervous system is closely related to it. Developing the dopamine receptor imaging agents of strong specificity and high affinity is a hot topic in the field of molecular nuclear medicine. The precursor(S)-3-[5-{(1-ethylpyrrolidin-2-yl) methylcarbamoyly}-2,3-dimethoxy phenyl] propyl-4-methyl benzemide was synthetized with vanillic acid methyl ester through seven steps, then radioactive compound ¹⁸F-(S)-N-{(1-ethylpyrrolidin-2-yl)methyl}-3-(3-fluropropyl)-4, 5-dimethoxy benzamide(¹⁸F-Fethypride) was radiolabeled by ¹⁸F through nucleophilic substitution reaction. Synthesis time was 35 min, radiochemical yield rate was (36.8±1.4)%, radiochemical purity of HPLC was 99%, radiochemical purity of TLC was 100%. Sterility test limulus reagent test K2.2.2 content detection and acute toxicity test were all qualified. Biodistribution test showed that ¹⁸F-Fethypride was metabolized through the liver, excreted through the renal, radioactivity gradually decreased with the extension of time. In brain tissue, radioactivity were mainly distributed in striatum, then in hippocampus, hypothalamus and cerebellum were lower. Striatum/cerebellum(Str/Cer) increased gradually, reached the highest at 90 min(10.68±0.35). The results showed that ¹⁸F-Fethypride was suit for the diagnosis of the nervous system diseases as dopamine receptor imaging agent.

Key words: Dopamine receptor imaging agent, 18F-labeling, Biodistribution

CLC Number:

O628.5⁺1

TrendMD:

LI Yinghua, WANG Bin, GUAN Feng, DAI Yuyin, LIN Chenghe, LU Jingbin, LIN Yingjie. Synthesis, Label and Biodistribution of ¹⁸F-Fethypride for Dopamine Receptor Imaging^†[J]. Chem. J. Chinese Universities, 2014, 35(3): 499.

Figures/Tables 4

References 20

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Tissue	ID(%)/g
Tissue	10 min	30 min	60 min	90 min	120 min
Heart	3.15±0.31	1.89±0.22	0.72±0.02	0.48±0.01	0.45±0.03
Lung	6.98±1.21	5.16±0.52	2.28±0.11	1.75±0.14	1.26±0.19
Liver	11.52±1.45	8.29±0.74	4.01±0.65	3.24±0.11	2.98±0.41
Spleen	8.68±0.59	4.35±0.13	1.24±0.10	1.03±0.07	1.01±0.08
Kidney	12.75±0.97	7.66±0.34	3.18±0.08	1.91±0.20	1.13±0.11
Striatum	4.16±0.58	2.96±0.51	2.71±0.33	2.35±0.27	1.13±0.12
Hippocampus	2.23±0.27	1.65±0.33	1.48±0.09	0.67±0.06	0.51±0.06
Thalamus	1.45±0.15	1.12±0.12	0.89±0.02	0.35±0.05	0.26±0.01
Cerebellum	1.21±0.22	0.84±0.10	0.36±0.01	0.22±0.03	0.12±0.01
Str/Cer	3.43±0.06	3.52±0.41	7.53±0.03	10.68±0.35	9.41±1.12

Tissue	ID(%)/g
Tissue	10 min	30 min	60 min	90 min	120 min
Heart	3.15±0.31	1.89±0.22	0.72±0.02	0.48±0.01	0.45±0.03
Lung	6.98±1.21	5.16±0.52	2.28±0.11	1.75±0.14	1.26±0.19
Liver	11.52±1.45	8.29±0.74	4.01±0.65	3.24±0.11	2.98±0.41
Spleen	8.68±0.59	4.35±0.13	1.24±0.10	1.03±0.07	1.01±0.08
Kidney	12.75±0.97	7.66±0.34	3.18±0.08	1.91±0.20	1.13±0.11
Striatum	4.16±0.58	2.96±0.51	2.71±0.33	2.35±0.27	1.13±0.12
Hippocampus	2.23±0.27	1.65±0.33	1.48±0.09	0.67±0.06	0.51±0.06
Thalamus	1.45±0.15	1.12±0.12	0.89±0.02	0.35±0.05	0.26±0.01
Cerebellum	1.21±0.22	0.84±0.10	0.36±0.01	0.22±0.03	0.12±0.01
Str/Cer	3.43±0.06	3.52±0.41	7.53±0.03	10.68±0.35	9.41±1.12

Synthesis, Label and Biodistribution of ¹⁸F-Fethypride for Dopamine Receptor Imaging^†

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No.	37 MBq group		18.5 MBq group		7.4 MBq group		Control group
No.	Weight 1/g	Weight 2/g	Weight 1/g	Weight 2/g	Weight 1/g	Weight 2/g	Weight 1/g	Weight 2/g
1	19	28	19	28	20	27	19	28
2	18	29	18	27	21	29	20	31
3	19	29	21	30	18	29	20	32
4	20	31	20	30	20	31	18	27
5	20	29	20	29	19	27	19	27

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