Objectives: Fixed tube modules like the TRACERLab FX_C-PRO or FX_MeI modules used for carbon-11 radiolabeling require extensive cleaning procedures between batches to prevent cross-contamination, which can impact operational simplicity as well as radiochemical yield (RCY) and purity (RCP). Cassette-based modules, like the FASTLab, limits cross contamination by using single-use cassettes preventing significant decline in RCY and RCP due to inadequate cleaning.¹ The [¹¹C]PIB synthesis published by Nair and colleagues demonstrates that ¹¹C synthesis techniques used on a fixed tube module can also be adapted for a cassette-based module to improve workflow, tracer output, and decrease cross-contamination risks.¹ Herein, we build on this proof-of-concept and report the synthesis of several common ¹¹C radiotracers using a FASTLab module.

Methods: [¹¹C]CO₂ was produced using the ¹⁴N(p,α)¹¹C reaction (60 μA, 2-10 min irradiation). At end of beam 3.7-37 GBq, was delivered to a FX_C-PRO to produce either [¹¹C]CH₃I or [¹¹C]CH₃OTf, which were subsequently transferred to a FASTLab module with a preassembled cassette. Six tracers were labeled using one of the following methods: 1) resin ([¹¹C]choline (CHO)), 2) loop ([¹¹C]raclopride (RAC)), 3) reactor ([¹¹C]L-methionine (MET), [¹¹C]sarcosine (SAR), [¹¹C]carfentanil (CFN), or [¹¹C]PE2I (PE2I)). CHO was synthesized by loading precursor onto a CM resin and passing [¹¹C]CH₃I through the resin. RAC was synthesized using loop chemistry by passing [¹¹C]CH₃OTf through a preloaded 2 mL stainless steel HPLC loop, purified using SAX resin, and reformulated using a HLB resin. MET was synthesized by sparging dissolved precursor in the reactor with [¹¹C]CH₃I and purified by evaporation. SAR was synthesized using [¹¹C]CH₃I or [¹¹C]CH₃OTf by sparging dissolved precursor in a reactor, purifying and reformulated using a SAX resin. CFN and PE2I were synthesized using [¹¹C]CH₃OTf by sparging dissolved precursor in a reactor, purified and reformulated using a C2 resin, or by loading precursor directly onto a C2 resin (Fig 1). Analytical HPLC was performed to determine the RCP as previously described.²

Results: Six carbon-11 tracers, CHO, RAC, MET, SAR, CFN, and PE2I, were radiolabeled using a FASTLab module. RCP of all tracers was >90% (Fig 1). RCY varied from 1.22% to 28.8% depending on the ¹¹C synthon used ([¹¹C]CH₃I or [¹¹C]CH₃OTf), and the labeling method (resin, loop, reactor). Lower RCYs were attributed to unoptimized transfer of [¹¹C]CH₃OTf from the FX_C-PRO to the FASTLab, sometimes resulting in ≤50% loss of activity due to atmospheric water producing [¹¹C]CH₃OH, which was removed. For RAC, SAR, CFN, and PE2I, reduced yields were also attributed to purification process required to achieve >90% RCP. Additionally for SAR, [¹¹C]CH₃I was not reactive enough to produce satisfactory yields thus, [¹¹C]CH₃OTf is recommended. Although the direct loading of CFN and PE2I precursor onto the C2 resin could improve reactivity of the ¹¹C synthon, potential side reactions were observed leading to RCPs of 66% and 56%, respectively. Ultimately these tracers were more efficiently labeled using a reactor.  

Conclusions: ¹¹C-labeling of six clinically relevant tracers using [¹¹C]CH₃I and [¹¹C]CH₃OTf with resin, loop, and reactor methods, demonstrated the feasibility of adapting current synthesis techniques for cassette-based modules. This approach reinforces a direct delivery line with solid-phase extraction (SPE) to improve synthesis workflow and decrease cross-contamination. Additionally, for the synthesis of CFN, the use of cassettes better adheres to regulations for the handling and disposal of DEA regulated control substances. The synthesis of RAC using SPE purification, which previously required a semi-preparatory HPLC, demonstrates the possibility to translate additional tracers to a cassette-based module. With these initial tests, we intend to continue optimizing the production of these tracers so that a cassette-based module can be used for routine carbon-11 production with high RCY and RCP to improve the production workflow.

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Image/Figure Caption:

Figure 1: Labeling six Carbon-11 tracers using [¹¹C]CH₃I or [¹¹C]CH₃OTf with a resin, reactor, or loop method. 6 clinically relevant carbon-11 tracers were labeled using a cassette-based module, FASTLab 2. Each of the labeled tracer had RCP > 90%. Site of carbon-11 methylation is in red. RCP – radiochemical purity (using rHPLC), non-decay corrected RCY – radiochemical yield (calculated using predicted [¹¹C]CO₂ activity at EOB divided by calibrated activity at EOS).

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