Automated Synthesis of [11C]PiB via [11CH3OTf]-as Methylating Agent for PET Imaging of ß-Amyloid.
Curr Radiopharm
; 17(3): 302-311, 2024.
Article
in En
| MEDLINE
| ID: mdl-38454773
ABSTRACT
AIM:
Efficient synthesis of precursor from commercially available starting materials and automated radiosynthesis of [11C]PiB using commercially available dedicated [11C]- Chemistry module from the synthesized precursor.BACKGROUND:
[11C]PiB is a promising radiotracer for PET imaging of ß-Amyloid, advancing Alzheimer's disease research. The availability of precursors and protocols for efficient radiolabelling foster the applications of any radiotracer. Efficient synthesis of PiB precursor was performed using anisidine and 4-nitrobenzoyl chloride as starting materials in 5 steps, having addition, substitutions, and cyclization chemical methodologies. This precursor was used for fully automated radiosynthesis of [11C]PiB in a commercially available synthesizer, MPS-100 (SHI, Japan). The synthesized [11C]PiB was purified via solid-phase methodology, and its quality control was performed by the quality and safety criteria required for clinical use.METHODS:
The synthesis of desired precursors and standard authentic compounds started with commercially available materials with 70-80% yields. The standard analytical methods were characterized all synthesized compounds. The fully automated [11C]-chemistry synthesizer (MPS-100) used for radiosynthesis of [11C]PiB with [11C]CH3OTf acts as a methylating agent. For radiolabelling, varied amounts of precursor and time of reaction were explored. The resulting crude product underwent purification through solid-phase cartridges. The synthesized radiotracer was analyzed using analytical tools such as radio TLC, HPLC, pH endo-toxicity, and half-life.RESULTS:
The precursor for radiosynthesis of [11C]PiB was achieved in excellent yield using simple and feasible chemistry. A protocol for radiolabelling of precursor to synthesized [11C]PiB was developed using an automated synthesizer. The crude radiotracer was purified by solid-phase cartridge, with a decay-corrected radiochemical yield of 40±5% and radiochemical purity of more than 97% in approx 20 minutes (EOB). The specific activity was calculated and found in a 110-121 mCi/µmol range.CONCLUSION:
A reliable methodology was developed for preparing precursor followed by fully automated radiolabeling using [11C]MeOTf as a methylating agent to synthesize [11C]PiB. The final HPLC-free purification yielded more than 97% radiochemical purity tracer within one radionuclide half-life. The method was reproducible and efficient for any clinical center.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiazoles
/
Carbon Radioisotopes
/
Amyloid beta-Peptides
/
Radiopharmaceuticals
/
Positron-Emission Tomography
/
Alzheimer Disease
/
Aniline Compounds
Limits:
Humans
Language:
En
Journal:
Curr Radiopharm
Year:
2024
Document type:
Article
Affiliation country:
India
Country of publication:
Emiratos Árabes Unidos