A New Approach to Synthesizing Carbon-11-PBR28 and its Clinical Validation in ALS Patients.

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

Methods: [11C]PBR28 has been synthesized using an HPLC-based and cartridge-based purification technique in the FX2C chemistry module. All necessary quality controls were performed and compared. We injected 350 ± 20 MBq of the [11C]PBR28 intravenously into human patients (n = 6) diagnosed with amyotrophic lateral syndrome (ALS) and performed simultaneous PETMR dynamic imaging.

Results: The radiochemical purity was greater than 95% with both methods. The radiochemical yield was 11.8 ± 3.3%, and molar activity was 253 ± 20.9 GBq/μmol with a total synthesis time of 25 ± 2 min in the HPLC-based purification method. Whereas the radiochemical yield was 53.0 ± 3.6%, and molar activity was 885 ± 17.7 GBq/μmol with a total synthesis time of 12 ± 2 min in the cartridge-based purification method. We have compared PET-MR imaging of ALS limb onset (n =3) with ALS bulbar and limb onset (n =3), and there was a difference in time activity curves. The activity was higher in the precentral gyrus and cerebellum at 2.5 ± 0.5 min in bulbar cases with an SUV of 2.3 ± 0.3, whereas ALS limb onset showed the highest uptake at 0.5 ± 0.2 min with an SUV of 1.5 ± 0.2.

Conclusion: The cartridge-based method provided higher radiochemical yield and molar activity.