Skip to content
2000
Volume 18, Issue 3
  • ISSN: 1874-4710
  • E-ISSN: 1874-4729

Abstract

Introduction

Many studies have reported translocator protein (TSPO) overexpression in various neurological disorders. Carbon-11[11C]PBR28 is a widely used TSPO Positron Emission Tomography (PET) radiopharmaceutical. We compared HPLC-based purification with cartridge-based purification and performed PET-MR imaging in ALS patients.

Methods

[11C]PBR28 was synthesized using both an HPLC-based and cartridge-based purification technique on the FX2C chemistry module. We injected 350 ± 20 MBq of the [11C]PBR28 intravenously into the patients diagnosed with amyotrophic lateral syndrome (ALS) limb onset (n =3) and bulbar (n =3). Simultaneous PET-MR dynamic imaging was then performed.

Results

The radiochemical purity exceeded 95% with both methods. Using the HPLC-based method, the radiochemical yield was 11.8 ± 3.3%, molar activity was 253 ± 20.9 GBq/μmol, and the total synthesis time of 25 ± 2 minutes. In contrast, the cartridge-based method yielded a radiochemical yield of 53.0 ± 3.6%, a molar activity of 885 ± 17.7 GBq/μmol, and a total synthesis time of 12 ± 2 minutes. In imaging results, higher activity was observed in the precentral gyrus and cerebellum at 2.5 ± 0.5 minutes in bulbar-onset ALS cases, with a standardized uptake value (SUV) of 2.3 ± 0.3. In contrast, limb-onset ALS cases showed the highest uptake at 0.5 ± 0.2 minutes, with an SUV of 1.5 ± 0.2.

Discussion

The difference in SUV in bulbar and limb onset may be due to pathological changes.

Conclusions

The cartridge-based purification method provided higher radiochemical yield and molar activity as compared to the HPLC purification method.

Loading

Article metrics loading...

/content/journals/crp/10.2174/0118744710341203250220042349
2025-02-26
2025-11-16
Loading full text...

Full text loading...

References

  1. Zanotti-FregonaraP. PascualB. RizzoG. Head-to-head comparison of 11C-PBR28 and 18F-GE180 for quantification of the translocator protein in the human brain.J. Nucl. Med.2018598126010.2967/jnumed.117.20310929348317
    [Google Scholar]
  2. ZürcherN.R. LoggiaM.L. MullettJ.E. TsengC. BhanotA. RicheyL. HightowerB.G. WuC. ParmarA.J. ButterfieldR.I. DuboisJ.M. ChondeD.B. Izquierdo-GarciaD. WeyH.Y. CatanaC. HadjikhaniN. McDougleC.J. HookerJ.M. [11C]PBR28 MR–PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.Mol. Psychiatry20212651659166910.1038/s41380‑020‑0682‑z32076115
    [Google Scholar]
  3. OwenD.R. GuoQ. KalkN.J. ColasantiA. KalogiannopoulouD. DimberR. LewisY.L. LibriV. BarlettaJ. Ramada-MagalhaesJ. KamalakaranA. NuttD.J. PasschierJ. MatthewsP.M. GunnR.N. RabinerE.A. Determination of [(11)C]PBR28 binding potential in vivo: A first human TSPO blocking study.J. Cereb. Blood Flow Metab.201434698999410.1038/jcbfm.2014.4624643083
    [Google Scholar]
  4. HoareauR. ShaoX. HendersonB.D. ScottP.J.H. Fully automated radiosynthesis of [11C]PBR28, a radiopharmaceutical for the translocator protein (TSPO) 18kDa, using a GE TRACERlab FXC-Pro.Appl. Radiat. Isot.20127081779178310.1016/j.apradiso.2012.03.00622503515
    [Google Scholar]
  5. WangM. YoderK.K. GaoM. MockB.H. XuX.M. SaykinA.J. HutchinsG.D. ZhengQ.H. Fully automated synthesis and initial PET evaluation of [11C]PBR28.Bioorg. Med. Chem. Lett.200919195636563910.1016/j.bmcl.2009.08.05119716298
    [Google Scholar]
  6. Solingapuram SaiK.K. GageD. NaderM. MachR.H. MintzA. Improved automated radiosynthesis of [11C]PBR28.Sci. Pharm.201583341342710.3797/scipharm.1505‑0626839827
    [Google Scholar]
  7. PeesA. ChasséM. LindbergA. VasdevN. Recent developments in carbon-11 chemistry and applications for first-in-human PET studies.Molecules202328393110.3390/molecules2803093136770596
    [Google Scholar]
  8. QuW. HuB. BabichJ.W. WaterhouseN. DooleyM. PonnalaS. UrgilesJ. A general 11C-labeling approach enabled by fluoride-mediated desilylation of organosilanes.Nat. Commun.2020111173610.1038/s41467‑020‑15556‑732269227
    [Google Scholar]
  9. DahlK. HalldinC. SchouM. New methodologies for the preparation of carbon-11 labeled radiopharmaceuticals.Clin. Transl. Imaging20175327528910.1007/s40336‑017‑0223‑128596949
    [Google Scholar]
  10. JoshiR.K. GoudN.S. NagarajC. KumarD. RG. RaoN.P. DhawanA. BhattacharyaA. MangaloreS. BharathR.D. KumarP. Radiosynthesis challenges of 11C and 18F-labeled radiotracers in the FX2C/N tracerlab and their validation through PET-MR imaging.Appl. Radiat. Isot.202116810948610.1016/j.apradiso.2020.10948633153893
    [Google Scholar]
  11. KwonH.S. KohS.H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes.Transl. Neurodegener.2020914210.1186/s40035‑020‑00221‑233239064
    [Google Scholar]
  12. ZhangW. XiaoD. MaoQ. XiaH. Role of neuroinflammation in neurodegeneration development.Signal Transduct. Target. Ther.20238126710.1038/s41392‑023‑01486‑537433768
    [Google Scholar]
  13. HerranzE. LouapreC. TreabaC.A. GovindarajanS.T. OuelletteR. MangeatG. LoggiaM.L. Cohen-AdadJ. KlawiterE.C. SloaneJ.A. MaineroC. Profiles of cortical inflammation in multiple sclerosis by 11 C-PBR28 MR-PET and 7 Tesla imaging.Mult. Scler.202026121497150910.1177/135245851986732031368404
    [Google Scholar]
  14. AlshikhoM.J. ZürcherN.R. LoggiaM.L. CernasovP. ReynoldsB. PijanowskiO. ChondeD.B. Izquierdo GarciaD. MaineroC. CatanaC. ChanJ. BabuS. PaganoniS. HookerJ.M. AtassiN. Integrated magnetic resonance imaging and [ 11 C]‐PBR28 positron emission tomographic imaging in amyotrophic lateral sclerosis.Ann. Neurol.20188361186119710.1002/ana.2525129740862
    [Google Scholar]
  15. KreislW.C. LyooC.H. LiowJ.S. WeiM. SnowJ. PageE. JenkoK.J. MorseC.L. ZoghbiS.S. PikeV.W. TurnerR.S. InnisR.B. 11C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease.Neurobiol. Aging201644536110.1016/j.neurobiolaging.2016.04.01127318133
    [Google Scholar]
  16. JucaiteA. CselényiZ. KreislW.C. RabinerE.A. VarroneA. CarsonR.E. RinneJ.O. SavageA. SchouM. JohnströmP. SvenningssonP. RascolO. MeissnerW.G. BaroneP. SeppiK. KaufmannH. WenningG.K. PoeweW. FardeL. Glia imaging differentiates multiple system atrophy from parkinson’s disease: A positron emission tomography study with [11 C] PBR28 and machine learning analysis.Mov. Disord.202237111912910.1002/mds.2881434609758
    [Google Scholar]
  17. ZürcherN.R. LoggiaM.L. LawsonR. ChondeD.B. Izquierdo-GarciaD. YasekJ.E. AkejuO. CatanaC. RosenB.R. CudkowiczM.E. HookerJ.M. AtassiN. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28.Neuroimage Clin.2015740941410.1016/j.nicl.2015.01.00925685708
    [Google Scholar]
/content/journals/crp/10.2174/0118744710341203250220042349
Loading
/content/journals/crp/10.2174/0118744710341203250220042349
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): carbon-11; microglial activation; neuroinflammation; PBR-28; PET imaging; radiochemistry; TSPO
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test