BackgroundOverexpression of prostatic membrane antigen (PSMA) is associated with the progression and prognosis of prostate cancer. There are numerous studies using this peptide with the 68Ga radionuclide. Previous methods to synthetize 18F–labeled PSMA ligands with complexes [18F]AlF2+ have been achieved. However, these reported syntheses were performed manually, using small volumes. Therefore it is only possible to have the radiopharmaceutical on a small scale, for use in preclinical studies. 18F–labelled tracers allow higher doses increasing the number of examined patients. In addition, late images can be acquired in the case of uptake in lymph nodes, to discard inflammation. It is important to transfer the manual synthesis to an automatic module, producing a batch of the radiopharmaceutical with high activity in a safe and effective way. The aim of this work was to optimize the labeling of [18F]AlF-[GLU-UREA-LYS(AHX)-HBED-CC] in a Tracerlab FXFN® (GE) platform.ResultsThe labeling up to the reactor corroborates the formation of the complex [18F]AlF-PSMA. After purification by HPLC, the radiopharmaceutical was achieved with a radiochemical purity higher than 90%. The quality control of the final product fulfilled all the requirements in agreement with USP, such as radiochemical purity (greater than 90%) and residual solvents. [18F]AlF-PSMA was obtained with a yield of 18 ± 3% (n = 7), not decay corrected (NCD) starting off from 500 to 2000 mCi the 18F and with a radiochemical purity of 95 ± 3% (n = 7). The product verified stability in the final formulation vial during 4 hs and in human plasma up to 1 h.ConclusionThe proposed method allowed the production of [18F]AlF-PSMA with suitable radiochemical purity in a commercial platform. High activities were achieved, with a simple and robust methodology appropriate for clinical purposes.
In this practitioner protocol, the optimization of the radiochemical synthesis of [18F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%–45% ndc). The other important improvement is the reduction of the required concentration of H2SO4 avoiding the production of high concentrations of acidic vapors that can deteriorate the module. Purification was achieved by solid phase extraction, and the required adaptation of an external heating plate to the module to evaporate the ethanol is also described. The product was obtained with high radiochemical purity and fulfilled all the requirements of current Good Manufacturing Practice (cGMP). The final product is formulated as a sterile, pyrogen‐free solution suitable for human injection. To the best of our knowledge, this is the first report of FES production using this type of module.
Herein we present the evaluation of 11C-labeled-maleimides as radiotracers for positron emission tomography imaging of GSK-3 associated with Alzheimer′s disease (AD). 3-Acetyl-4-(1-[11C]-methyl-1H-indol-3-yl)[1H]pyrrole-2,5-dione ([11C]-2) was obtained by direct methylation using [11C]-CH3I and Cs2CO3 in DMF with a 31 ± 4% radiochemical yield and a radiochemical purity of 97.7 ± 0.8%. [11C]-2 was stable both in its final formulation and in human plasma for 120 min and had a plasma protein binding of 70 ± 1% and a LogD7.4 value of 1.84 ± 0.04. [11C]-2 ex vivo biodistributions in healthy animals demonstrated significant brain uptake and retention, showing its ability to penetrate the intact blood–brain barrier. In vivo PET imaging in mice bearing AD showed, with respect to normal animals, significant differences in uptake in the hypothalamus, the striatum, and the amygdala and a significant increase in amygdala uptake in later stages of the pathology. These results are very promising, and further studies are being performed for a complete validation of this compound as novel tracer for AD.
With the objective to develop a potential 99mTc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99mTc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture. All complexes exhibited considerable uptake in AR-positive cells, which could be blocked by an excess of flutamide. The efflux from the cells was moderate. They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to 99mTc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells.
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