Fully automated synthesis of PET TSPO radioligands [11C]DAA1106 and [18F]FEDAA1106.

[(11)C]DAA1106 was prepared by O-[(11)C]methylation of DAA1123 with [(11)C]CH(3)OTf and NaH in CH(3)CN at 80°C and isolated by HPLC combined with SPE purification in 60-70% decay corrected radiochemical yield. [(18)F]FEDAA1106 was synthesized by the nucleophilic substitution of tosyloxy-FEDAA1106 in DMSO with K[(18)F]F/Kryptofix 2.2.2 at 140°C and isolated by HPLC combined with SPE purification in 30-60% decay corrected radiochemical yield. The specific activity for [(11)C]DAA1106 and [(18)F]FEDAA1106 was 370-740GBq/μmol and 37-222GBq/μmol at EOB, respectively.

Wang M ，Gao M ，Zheng QH 《-》

Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor with PET.

[(18)F]PBR111 and [(18)F]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [(18)F]PBR111 and [(18)F]PBR102 in the Tracerlab FX(FN) (30±2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MX(FDG) (25±2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was >99% and specific activity was >150GBq/μmol after less than 60min of preparation time.

Bourdier T ，Pham TQ ，Henderson D ，Jackson T ，Lam P ，Izard M ，Katsifis A ... -  《-》

Synthesis of [11C]FEDAA1106 as a new PET imaging probe of peripheral benzodiazepine receptor expression.

Wang M ，Gao M ，Hutchins GD ，Zheng QH ... -  《-》

An improved synthesis of dopamine D2/D3 receptor radioligands [11C]fallypride and [18F]fallypride.

Improved syntheses of dopamine D(2)/D(3) receptor radioligands [(11)C]Fallypride and [(18)F]Fallypride are reported. The phenolic precursor (9) for C-11 labeling and the Fallypride (10) reference standard were synthesized from the starting material 2-hydroxy-3-methoxy-5-(2-propenyl)benzoic acid methyl ester (1) in 7 and 8 steps with 16% and 5% overall chemical yields, respectively. The tosylated precursor (15) for F-18 labeling was synthesized from compound 1 in 5 steps with 32% overall chemical yield. An alternate synthetic approach for Fallypride has been developed using the same starting material 1 in 5 steps with 26% overall chemical yield. [(11)C]Fallypride ([(11)C]10) was prepared by O-[(11)C]methylation of the phenolic precursor with [(11)C]methyl triflate and purified with a semi-preparative HPLC method in 50-60% radiochemical yield, decay corrected to end of bombardment (EOB), based on [(11)C]CO(2), and 370+/-185 GBq/micromol specific radioactivity at EOB. [(18)F]Fallypride ([(18)F]10) was prepared by nucleophilic substitution of the tosylated precursor with K[(18)F]F/Kryptofix 2.2.2 and HPLC combined with solid-phase extraction (SPE) purification in variable (up to 50%) decay corrected radiochemical yield from K[(18)F]F and 111-222 GBq/micromol specific activity at EOB.

Gao M ，Wang M ，Mock BH ，Glick-Wilson BE ，Yoder KK ，Hutchins GD ，Zheng QH ... -  《-》

Synthesis of [¹¹C]PBR06 and [¹⁸F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO).

The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [(18)F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [(11)C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [(11)C]PBR06 was prepared by O-[(11)C]methylation of desmethyl-PBR06 with [(11)C]CH(3)OTf in CH(3)CN at 80°C under basic condition and isolated by HPLC combined with SPE purification with 40-60% decay corrected radiochemical yield and 222-740 GBq/μmol specific activity at EOB. On the similar grounds, [(18)F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [(18)F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140°C with K[(18)F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20-60% decay corrected radiochemical yield, >99% radiochemical purity, 87-95% chemical purity, and 37-222 GBq/μmol specific activity at EOB. Radiosynthesis of [(18)F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.

Wang M ，Gao M ，Miller KD ，Zheng QH ... -  《-》