Dataset Information

Synthesis and ¹⁸F-radiolabeling of thymidine AMBF₃ conjugates.

ABSTRACT: In pursuit of ¹⁸F-labeled nucleosides for positron emission tomography (PET) imaging, we report on the chemical and radiochemical synthesis of two thymidine (dT) analogs, dT-C⁵-AMBF₃ and dT-N³-AMBF₃, that are radiofluorinated by isotope exchange (IEX) and studied as PET imaging agents in mice with tumor xenografts. dT-C⁵-AMBF₃ shows preferential, and tumor-specific, uptake over dT-N³-AMBF₃. This work provides a new synthetic method in order to access new nucleoside tracers for PET imaging.

SUBMITTER: Wong AAWL

PROVIDER: S-EPMC7578706 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Synthesis and 18F-radiolabeling of thymidine AMBF3 conjugates.

Wong Antonio A W L AAWL Lozada Jerome J Lepage Mathieu L ML Zhang Chengcheng C Merkens Helen H Zeisler Jutta J Lin Kuo-Shyan KS Bénard François F Perrin David M DM

RSC medicinal chemistry 20200423 5

In pursuit of 18F-labeled nucleosides for positron emission tomography (PET) imaging, we report on the chemical and radiochemical synthesis of two thymidine (dT) analogs, dT-C5-AMBF3 and dT-N3-AMBF3, that are radiofluorinated by isotope exchange (IEX) and studied as PET imaging agents in mice with tumor xenografts. dT-C5-AMBF3 shows preferential, and tumor-specific, uptake over dT-N3-AMBF3. This wo ...[more]

PMID: 33479658

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Project description:The efficient radiosynthesis of biomolecules utilizing minute quantities of maleimide substrate is important for availability of novel peptide molecular imaging agents. We evaluated both 3-18F-fluoropropane-1-thiol and 2-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)ethane-1-thiol (18F-fluoro-PEG4 thiol) as prosthetic groups for radiolabeling under physiological conditions. The precursor employed a benzoate for protection of the thiol and an arylsulfonate leaving group. The radiofluorination was fully automated on an Eckert & Ziegler synthesis system using standard Kryptofix222/K2CO3 conditions. In order to minimize the amount of biological molecule required for subsequent conjugation, the intermediates, S-(3-18F-fluoropropyl) benzothioate and 18F-fluoro-PEG4 benzothioate, were purified by HPLC. The intermediates were isolated from the HPLC in yields of 37-47% and 28-35%, respectively, and retrieved from eluate using solid phase extraction. Treatment of the benzothioates with sodium methoxide followed by acetic acid provided the free thiols. The desired maleimide substrate in acetonitrile or phosphate buffer was then added and incubated at room temperature for 15 min. The final radiolabeled bioconjugate was purified on a separate HPLC or NAP-5 column. Maleimides utilized for the coupling reaction included phenyl maleimide, an Evans Blue maleimide derivative, a dimeric RGDfK maleimide (E[c(RGDfK)]2), two aptamer maleimides, and PSMA maleimide derivative. Isolated radiochemical yields (non-decay corrected) of maleimide addition products based on starting 18F-fluoride ranged from 6 to 22% in a synthesis time of about 90 min. 18F-thiol prosthetic groups were further tested in vivo by conjugation to E[c(RGDfK)]2 maleimide in a U87MG xenograft model. PET studies demonstrated similar tumor accumulation of both prosthetic groups. 18F-fluoro-PEG4-S-E[c(RGDfK)]2 displayed a somewhat favorable pharmacokinetics compared to 18F-fluoropropyl-S-E[c(RGDfK)]2. Bone uptake was low for both indicating in vivo stability.

Dataset Information

Synthesis and ¹⁸F-radiolabeling of thymidine AMBF₃ conjugates.

Publications

Synthesis and <sup>18</sup>F-radiolabeling of thymidine AMBF<sub>3</sub> conjugates.

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