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

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.

[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.

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.

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

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