This report describes the development of a Zn(OTf)₂‐mediated method for converting α‐tertiary haloamides to the corresponding fluorine‐18 labelled α‐tertiary fluoroamides with no‐carrier‐added [¹⁸F]tetramethylammonium fluoride. 1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C−H radiofluorination process using N‐sulphonyloxyamide substrates.

The success of multiple nuclear medicine radiotherapeutics in treating cancer requires an increased supply of companion diagnostic imaging agents radiolabeled with gallium-68. Cyclotron production addresses the need for access to gallium-68 and has been validated for use with commercially produced sterile kits. For novel research tracers undergoing translational studies (IND or RDRC), developing and purchasing sterile kits is time- and cost-prohibitive. An on-cassette labeling method with terminal filtration allows non-sterile kits to be fabricated in-house, simplifying workflow and allowing multiple PET imaging agents to be evaluated using the same kit (i.e., parts, reagents, and timelist) with minimal variation. Using modified GE gallium chloride cassettes, four diverse clinically relevant tracers (DOTA-TOC, FAPI-04, pentixafor, and PSMA-11) were radiolabeled with gallium-68 to evaluate the approach using DOTA and HBED-CC chelator types. The tracers were all formulated according to established FDA-approved formulations and sterile-filtered using a PVDF membrane. The automated procedure is robust, tolerating DOTA and HBED-CC chelators, and can be used to screen numerous gallium-68 agents for rapid translation to clinical use.

Copper-mediated radiolabelling has revolutionised how (hetero)aromatic imaging agents are prepared for positron emission tomography (PET). Despite advancements, this radiochemistry fails to address critical stability, reactivity, and toxicity concerns encountered in many labelling systems, which are paramount for safely and reproducibly generating patient radiomedicines. To overcome these limitations, a copper-mediated 11C-cyanation reaction is presented that leverages heptamethyltrisiloxanes as (hetero)aryl nucleophiles. Rapid ipso-radiocyanation occurs in conversions that surpass related precursors while offering stability and toxicity advantages. Preliminary mechanistic data suggests that a difluoro(methyl)aryl silane may be generated prior to transmetallation. Multiple bioactive scaffolds relevant to (pre)clinical PET were labelled to showcase the broader significance of this protocol, including an automated radiosynthesis of a -opioid receptor antagonist currently under clinical investigation. Overall, adopting aryl silane precursors will augment radiochemical space and support the production of PET nuclear medicines.

This report describes the development of a Zn(OTf)₂‐mediated method for converting α‐tertiary haloamides to the corresponding fluorine‐18 labelled α‐tertiary fluoroamides with no‐carrier‐added [¹⁸F]tetramethylammonium fluoride. 1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C−H radiofluorination process using N‐sulphonyloxyamide substrates.