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Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme

This work aims to develop a stereoselective enzymatic alternative for the radiosynthesis of [11C](S,S)-S-ade-nosylmethionine ([11C](S,S)-SAM), a potential PET-CT radiotracer for monitoring particularly aggressive prostate tumors. Conventional synthesis of this compound has been carried out at Urugua...

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Hovedforfatter: Diego, Umpiérrez Puchalvert (author)
Andre forfattere: Florencia, Zoppolo (author), Manuela Bentura (author), Agustin, Castilla (author), Eduardo, Savio (author), Sonia, Rodríguez Giordano (author), Gabriela, Irazoqui (author)
Format: article
Sprog:engelsk
Udgivet: 2024
Fag:
Enzymatic radiosynthesis
SAM
S-adenosylmethionine
Methionine adenosyltransferase
Immobilized enzyme
Prostate cancer radiotracer
Stereospecificity
Ciencias Naturales y Exactas
Ciencias Químicas
Online adgang:https://hdl.handle.net/20.500.12381/5578
https://doi.org/10.1016/j.procbio.2024.12.006
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Summary:This work aims to develop a stereoselective enzymatic alternative for the radiosynthesis of [11C](S,S)-S-ade-nosylmethionine ([11C](S,S)-SAM), a potential PET-CT radiotracer for monitoring particularly aggressive prostate tumors. Conventional synthesis of this compound has been carried out at Uruguayan Center of Molecular Imaging, resulting in an almost racemic mixture 53:47 ratio of (R,S) to (S,S) isomer. Producing the radiotracer in an optically pure form is a requirement for administration to humans and additionally it would enhance diagnostic sensitivity when administered to the patient. The main challenges were designing a biocatalyst capable of withstanding the harsh conditions of the radiotracer synthesis module and achieving the reaction in a very short time due to the rapid decay of 11C. A mutant of E. coli methionine adenosyltransferase (I303V MAT) with enhanced SAM synthesis was cloned, expressed, and immobilized on agarose using an irreversible covalent isourea bond. This immobilized enzyme synthesized [11C](S,S)-SAM from [11C]L-methionine in an automated module, with the labeled methionine produced in situ from [11C]CH3I and L-homocysteine thiolactone. The product was obtained with an enantio and diasteromeric excess greater than 99 % and average conversion of 80 %. The reuse of the immobilized enzyme was studied, showing that after three cycles of reuse the radiosynthesis performance remained unchanged.

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