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  • Our module is designed to

    2019-07-11

    Our module is designed to allow in-process measurement of [C]-tracer molar activity (MA, GBq/μmol at EOB) using a Tideglusib detector with a UV detector at the outlet of the HPLC-portion of the system. In the HPLC chromatogram, peak analysis of the chromatographic data utilized PeakSimple software (SRI Instruments, Las Vegas, NV). Immediately following elution of the product peak, the chromatographic data are exported to PeakSimple readable files, and the area of the radioactivity peak is converted to GBq – mCi at EOB by comparison to a reference calibration curve previously constructed using the same detector, loop column, mobile phase and flow rate. The mass peak from the UV chromatogram (without decay correction) is similarly compared to a standard curve made at the same UV wavelength, mobile phase and flow rate. Simple division of the total EOB radioactivity peak (in GBq – mCi) by the total mass peak (in nmoles) gives MA at EOB in GBq – Ci/μmol. For the reported syntheses, product MA was in a range of 370–740 GBq/μmol at EOB. The factors that affect the EOB MA significantly to lead to such a wide range have been discussed in our previous works., , The general methods to increase MA have been described as well, and the MA of our [C]-tracers is significantly improved., , The ‘wide range’ of MA we reported is for the same [C]-tracer produced in different days, because very different [C]-target and [C]-radiosynthesis unit situations would make MA in a wide range. For a [C]-tracer produced in the same day, the MA of the same tracer in different production runs will be in a small range, because [C]-target and [C]-radiosynthesis unit would not be much different in the same day. Likewise, the methods to minimize such wide range of MA from practice perspective have been provided in our previous works., , At the end of synthesis (EOS), the MA of [C]-tracer was determined again by analytical RP HPLC, calculated, decay corrected to EOB, and based on [C]CO, which was in agreement with the ‘on line’ determined value. In this work, semi-preparative HPLC was used for purification, thus the MA of [C]-tracer was assessed by both semi-preparative HPLC (during synthesis) and analytical HPLC (EOS). Chemical purity and radiochemical purity were determined by analytical HPLC. The chemical purity of the precursor and reference standard was >93%. The radiochemical purity of the target tracer was >99% determined by radio-HPLC through γ-ray (PIN diode) flow detector, and the chemical purity of the target tracer was >90% determined by reversed-phase HPLC through UV flow detector. The octanol-water partition coefficient (commonly expressed as Log P) is an important physical parameter directly correlated with the biological activities of a wide variety of organic compounds., Log P provides an assessment of lipophilicity that often correlates with a compound’s ability to penetrate the blood brain barrier (BBB). Log P can be determined experimentally by liquid-liquid extraction and by HPLC and can also be theoretically calculated from parameters related to the structure of molecules. We obtained Log P and calculated Log P (CLog P) values of carbon-11-labeled CK1 inhibitors [C] and [C] in comparison with [C]PIB, [F]Amyvid, [C]PBB3 and [F]T807 () from ChemDraw Professional 15.1 (ChemOffice), and the data are listed in . Log P data of [C] and [C] (3.60–3.66) are in the range of Log P data of [C]PIB, [F]Amyvid, [C]PBB3 and [F]T807 (2.25–4.09), which are PET AD imaging agents in clinical evaluation. These data suggest [C] and [C] have appropriate lipophilicity to pass the BBB for brain uptake. The stability of the labeled tracers [C] and [C] was evaluated by analytical HPLC from EOS up to 3 h, one injection of the tracer solution in EtOH/saline onto HPLC column per hour. The HPLC chromatograms showed [C] and [C] were stable without decomposition. The experimental details and characterization data for compounds – and for the tracers [C] and [C] are given.