The need for UDP-GlcNAc for glycoprotein synthesis also ..
Bombesin receptor ligand analogues have been used in clinical studies however the high potency of agonists brings up challenges requiring synthesis with high specific radioactivity in order to exclude pharmacological effects. Antagonists even though they do not internalize have shown improved imaging capabilities. Given recent achievements in the design of antagonists and experience with SST analogues demonstrating advantages of antagonists, the future development will most likely move in the direction of bombesin antagonists.
Click Chemistry Publications - Scripps Research Institute
First generators were introduced in the late 1950s early 1960s and 68Ga-based imaging agents were available already from the 1970s but further progress was precluded by the absence of reliable sources of the generators as well as their properties and quality. During last decade PET has been recognized as a clinically relevant and valuable diagnostic technique providing quantitative information on the physiological status of a disease and possibility to perform a whole-body scan in a single examination. There are many interrelated factors that contributed to the clinical acceptance of PET in general and blossom of 68Ga/PET in particular. Technological aspects include achievements in improved sensitivity, resolution, accurate quantitation, and introduction of hybrid systems, PET-CT and PET-MRI; availability and increasing assortment of commercial 68Ge/68Ga generators; advances in biological research and biotechnology providing identification of biomarkers; accessibility of automated synthesizers for GMP compliant production of imaging agents. The automation may also provide possibility for the harmonized and standardized multicentre clinical studies that in turn will accelerate the introduction of new radiopharmaceuticals as well as their regulatory approval. Steady progress is being observed in PET radiopharmaceutical regulations and multicenter trials. The plausible correction and increase of the parent 68Ge breakthrough limit in the radiopharmaceutical preparation (European Pharmacopoeia) may together with the labelling methods of high selectivity towards 68Ga(III) at room temperature allow for kit type production at radiopharmacy practice and consequently even wider allocation and use of 68Ga-radiopharmaceuticals. The feasibility of PET-CT being cost-effective and cost-saving has been demonstrated, especially in combination with cheaper, as compared to cyclotron, generator produced 68Ga radionuclide. Further technological development might render cost reduction and consequently improve profitability and affordability. This in turn may stimulate investments in radiopharmaceutical research and development.
The invention of chemoselective methodologies is crucial to the execution of 'protecting-group-free' synthesis, and recent advances in this area are also highlighted.