The excitatory amino acid transporters (EAATs) play essential roles in regulating the synaptic concentration of the neurotransmitter glutamate in the mammalian central nervous system. To date, five subtypes have been identified, named EAAT1–5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively. In this paper, we present the design, synthesis, and pharmacological evaluation of seven 7-N-substituted analogues of UCPH-101/102. Analogue 9 inhibited EAAT1 in the micromolar range (IC₅₀ value 20 μM), whereas analogues 8 and 10 were inactive (IC₅₀ values >100 μM). The diastereomeric pairs 11a/11b and 12a/12b were separated by HPLC and the absolute configuration assigned by VCD technique in combination with ab initio Hartree–Fock calculations. Analogues 11a (RS-isomer) and 12b (RR-isomer) inhibited EAAT1 (IC₅₀ values 5.5 and 3.8 μM, respectively), whereas analogues 11b (SS-isomer) and 12a (SR-isomer) failed to inhibit EAAT1 uptake (IC₅₀ values >300 μM).

Background The radiofluorinated levodopa analogue 6-[18F]F-l-DOPA (3,4-dihydroxy-6-18F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [18F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site. Methods Data from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed. Results The electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants. Conclusion For most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.

Alzheimer’s disease (AD) is a neurodegenerative disorder with increasing global prevalence and accounts for over half of all dementia cases. Early diagnosis is paramount for not only the management of the disease, but also for the development of new AD treatments. The current golden standard for diagnosis is performed by positron emission tomography (PET) scans with the tracer [¹¹C]Pittsburg Compound B ([¹¹C]PiB), which targets amyloid beta protein (Aβ) that builds up as plaques in the brain of AD patients. The increasing demand for AD diagnostics is in turn expected to drive an increase in [¹¹C]PiB-PET scans and the setup of new [¹¹C]PiB production lines at PET centers globally. Here, we present the [¹¹C]PiB production setups, experiences, and use from four Danish PET facilities and discuss the challenges and potential pitfalls of [¹¹C]PiB production. We report on the [¹¹C]PiB production performed with the 6-OH-BTA-0 precursor dissolved in either dry acetone or 2-butanone and by using either [¹¹C]CO₂ or [¹¹C]CH₄ as ¹¹C- precursors on three different commercial synthesis modules: TracerLab FX C Pro, ScanSys, or TracerMaker. It was found that the [¹¹C]CO₂ method gives the highest radioactive yield (1.5 to 3.2 GBq vs. 0.8 ± 0.3 GBq), while the highest molar activity (98.0 ± 61.4 GBq/μmol vs. 21.2 to 95.6 GBq/μmol) was achieved using [¹¹C]CH₄. [¹¹C]PiB production with [¹¹C]CO₂ on a TracerLab FX C Pro offered the most desirable results, with the highest yield of 3.17 ± 1.20 GBq and good molar activity of 95.6 ± 44.2 GBq/μmol. Moreover, all reported methods produced [¹¹C]PiB in quantities suitable for clinical applications, thus providing a foundation for other PET facilities seeking to establish their own [¹¹C]PiB production.

[¹¹C]Choline ([¹¹C]CHO) has reemerged as a radiopharmaceutical tracer for positron emission tomography (PET) diagnostics and optimized synthesis setups are thus needed to meet the increased demand, often on existing production lines. Originally, [¹¹C]CHO has experienced a decline in use for PET diagnostics, particularly in prostate cancer imaging due to radiopharmaceuticals with higher target specificity. However, recent studies have demonstrated superior sensitivity and diagnostic accuracy of [¹¹C]CHO for localizing autonomous adenomas in primary hyperparathyroidism (PHPT) compared to conventional ⁹⁹ᵐTc-sestamibi scintigraphy. The PET-scan is used prior to surgery, but not for the diagnosis of PHPT. The patient compliance is high due to the relatively short time in the scanner. With this renewed clinical relevance, optimization of [¹¹C]CHO synthesis is warranted, as standard production protocols typically yield only 2.5–3.0 GBq. In this study, three critical steps in the synthesis process on a TracerMaker module were systematically evaluated and optimized. (1) Extending the irradiation time from 25 to 42 minutes produced no significant increase in radiochemical yield (RCY). (2) Increasing the precursor, dimethylaminoethanol (DMAE) loading volume to 150 µL divided across two serially connected Sep-Pak Accell CM Plus Light cartridges resulted in a twofold RCY increase but also elevated residual DMAE levels in the final product. (3) Increasing washing volumes of ethanol and water did not improve purification efficiency; however, replacing the two stacked cartridges (2 × 130 mg) with a single cartridge containing a higher sorbent mass (360 mg) achieved effective DMAE removal while maintaining high RCY. These findings demonstrate a practical route for optimizing [¹¹C]CHO synthesis to meet the growing clinical demand of [¹¹C]CHO for imaging of PHPT.