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Copper-free click bioconjugation of technetium-99m complexes using strained cyclononyne derivatives
- Source :
- Dalton Transactions 52(2023), 3024-3032
- Publication Year :
- 2023
- Publisher :
- Royal Society of Chemistry (RSC), 2023.
-
Abstract
- Click chemistry, and in particular copper-free click reactions, have gained growing interest for radiolabeling purposes in the field of radiopharmaceutical sciences. [99mTc][Tc(CO)3(H2O)3]+ is an excellent starting complex for radiolabeling of biomolecules under mild conditions. A new chelator, investigated for the copper-free strain-promoted cycloaddition, was synthesized containing the 2,2’-dipicolylamine (DPA) moiety for the 99mTc-tricarbonyl core and compared with a chelator based on activated esters for conventional radiolabeling. For the copper-free click labeling procedure, a DPA containing 4,8-diazacyclononyne moiety was prepared from a sulfonyl-modified diamide (four steps, 64% yield) ensued by the Nicholas reaction with butyne-1,3-diol. The 99mTc-DPA-DACN-complex was prepared with a radiochemical conversion (RCC) of 89% after 30 min. The following SPAAC reaction with an azide-functionalized PSMA molecule was performed within 4 hours to obtain the PSMA (prostate-specific membrane antigen) targeting 99mTc-complex with 79% RCC and without side products. For comparison, a second DPA-chelator based on a tetrafluorophenyl (TFP) ester was prepared (three steps, 64% yield) and was successfully radiolabeled with [[99mTc]Tc(CO)3(H2O)3]+ in 89% RCC after 20 min and >99% radiochemical purity after separation using an RP18 cartridge. The subsequent conjugation of an amine-functionalized PSMA targeting molecule was performed with 23% RCC after 150 min. Two other unknown side products were observed indicating hydrolysis of the TFP ester during the labeling. All nonradioactive Re(CO)3 complexes were synthesized from (Et4N)2[ReBr3(CO)3] (91% yield for the natRe-DPA-TFP ester, 76% yield for the natRe-DPA-DACN) and characterized to confirm the identity of the 99mTc-complexes.
- Subjects :
- Inorganic Chemistry
Technetium-99m
kupferfrei
Click Chemie
Subjects
Details
- ISSN :
- 14779234 and 14779226
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Dalton Transactions
- Accession number :
- edsair.doi.dedup.....8e043a36f6ace83f96034fc0b3b9e11a