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. 2009 Oct 1;19(19):5636-9.
doi: 10.1016/j.bmcl.2009.08.051. Epub 2009 Aug 15.

Fully automated synthesis and initial PET evaluation of [11C]PBR28

Min Wang  1 , Karmen K Yoder, Mingzhang Gao, Bruce H Mock, Xiao-Ming Xu, Andrew J Saykin, Gary D Hutchins, Qi-Huang Zheng
Affiliations

Fully automated synthesis and initial PET evaluation of [11C]PBR28

Min Wang et al. Bioorg Med Chem Lett. .

Abstract

Fully automated synthesis and initial PET evaluation of a TSPO radioligand, [11C]PBR28 (N-(2-[11C]methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide), are reported. These results facilitate the potential preclinical and clinical PET studies of [11C]PBR28 in animals and humans.

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Figures

Figure 1
Figure 1
Chemical structures of PET TSPO radioligands.
Scheme 1
Scheme 1
Synthesis of desmethyl-PBR28 and PBR28. Reagents, conditions, and yields: (a) phenol, K2CO3, DMF, 80°C, 97%; (b) SnCl2, conc. HCl, MeOH, 80°C, 92%; (c) for 3a: o-salicylaldehyde, 90°C, then NaBH4, MeOH, room temperature (rt), 91%; for 3b: o-anisaldehyde, 100°C; then NaBH4, MeOH, rt, 90%; (d) for 4a: acetyl chloride, DMAP, CH2Cl2, rt, then sat. LiOH, MeOH, rt, 84%; for 4b: acetyl chloride, DMAP, CH2Cl2, rt, 78%.
Scheme 2
Scheme 2
Alternate synthetic approach for PBR28. Reagents, conditions, and yields: (a) NaH, CH3I, DMF, rt, 36%.
Scheme 3
Scheme 3
Synthesis of [11C]PBR28. Reagents, conditions, and yields: (a) NaH, [11C]CH3OTf, CH3CN, 80 °C, 3 min, 70-80%.
Figure 2
Figure 2
[11C]PBR28-PET images in 2 TBI and 1 SHM rats. A. TBI.001. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. B. TBI.002. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. C. SHM.001. 40-90 min integrated image. Crosshairs positioned at roughly the same coordinates as in A and B. In this animal, there was no visible left-side lesion.
Figure 2
Figure 2
[11C]PBR28-PET images in 2 TBI and 1 SHM rats. A. TBI.001. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. B. TBI.002. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. C. SHM.001. 40-90 min integrated image. Crosshairs positioned at roughly the same coordinates as in A and B. In this animal, there was no visible left-side lesion.
Figure 2
Figure 2
[11C]PBR28-PET images in 2 TBI and 1 SHM rats. A. TBI.001. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. B. TBI.002. 40-90 min integrated image. Crosshairs positioned at putative site of lesion: left parietal cortex. Green arrows indicated ROIs in the rat brain. C. SHM.001. 40-90 min integrated image. Crosshairs positioned at roughly the same coordinates as in A and B. In this animal, there was no visible left-side lesion.
See this image and copyright information in PMC

References

    1. Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere J-J, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang M-R, Gavish M. Trends Pharmacol.Sci. 2006;27:402. - PubMed
    1. Wang M, Gao M, Hutchins GD, Zheng Q-H. Eur. J. Med. Chem. 2009;44:2748. - PubMed
    1. Benavides J, Fage D, Carter C, Scatton B. Brain Res. 1987;421:167. - PubMed
    1. Probst KC, Izquierdo D, Bird JLE, Brichard L, Franck D, Davis JR, Fryer TD, Richards HK, Clark JC, Davenport AP, Weissberg PL, Warburton EA. Nucl. Med. Biol. 2007;34:439. - PubMed
    1. Venneti S, Lopresti BJ, Wiley CA. Progr. Neurobiol. 2006;80:308. - PMC - PubMed

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