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Principles behind Radiopharmacy
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
The production of radiopharmaceuticals is a demanding process and involves several steps that are performed in a limited time frame of a few hours. These steps include radionuclide production (cyclotron bombardment), radiosynthesis, quality control, and release of the product for administration to patients. A schematic illustration of the workflow is shown in Figure 1.2. The various means to produce a radiopharmaceutical are outlined in section 1.4. The details of quality control (QC) in the production of radiopharmaceuticals can be found in the IAEA TECDOC series [10] and in Chapter 6. In general, QC procedures are always performed for manufactured products prior to patient administration. The main purpose of QC is to ensure that the radiopharmaceuticals are of acceptable quality in terms of purity, identity, and sterility and that they are safe before they are administered in humans.
Radiochemistry for Preclinical Imaging Studies
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Initially, imaging agents used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) were radioisotopes or basic modifications thereof (ions, very basic small molecules, or aggregates like colloids). Since then, modern synthetic radiochemistry has created a large and increasing choice of more complex radiotracer molecules. Radiochemistry nowadays can be considered one of the main motors of PET and SPECT research. To facilitate and promote a quicker, more widespread use of developed radiotracers in different imaging labs and clinics, radiosynthesis automation is another key advancement for nonmetal radiotracers.
Design of New Imaging Agents Using Positron-Emitting Radionuclides as the Reporter
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Poethko et al. have shown that the aromatic aldehyde is also useful and is a less complicated synthesis compared with the usual procedure for introducing a 18F through an active ester of 4-fluorobenzoic acid. The 18F is introduced into the aromatic ring by the same method, that is, displacement of the trimethyl ammonium group. Then the aldehyde is reacted with a aminooxypeptide to form the N-(4-[18F]fluorobenzylidene) oxime. This approach did require the formation of the aminooxypeptide, but this can be done in bulk before the radiosynthesis begins. This approach has been tested in vivo with a RGD analog and a somatostatin receptor binding peptide. Both showed good in vivo stability and favorable pharmacokinetics (70).
Synthetic methodologies and PET imaging applications of fluorine-18 radiotracers: a patent review
Published in Expert Opinion on Therapeutic Patents, 2022
Sridhar Goud Nerella, Ahana Bhattacharya, Pavitra S Thacker, Sanam Tulja
The remarkable 18F-radiotracer that has been widely used in clinical applications for three decades is [18F]FDG and regarded as a potential positron emission tomography (PET) imaging agent to detect various conditions in oncology, cardiology, and neurology [5]. Recently, the patent WO 2017/203,017 also reported a specific and rare application of [18F]FDG that it can also be labeled with Red Blood Cells to measure blood pool in living subjects, where it is briefly explained that how it reveals more clinical information through PET [6]. Various 18F-radiotracers are currently used for PET imaging studies in different conditions due to many advantages with fluorine-18 in comparison with other PET radionuclides [7]. It is considered as an ideal radionuclide for PET radiotracer development because the half-life of fluorine-18 is 109.8 min, which is higher than other positron emitting radionuclides. Fluorine-18 is well tolerated for long-run radiosynthesis, and easily accessible for transportation to different clinical PET centers and research institutions because the establishment of cyclotron facility is associated with high cost and maintenance; therefore, 18F-radiotracers fulfill the needs of biomedical researchers and clinicians for PET imaging studies with a longer half-life. Several industries are developing cGMP compliance 18F-radiopharmaceuticals in a cyclotron-based commercial site and distributing them near PET clinical centers [8].
Biophysical and chemical stability of surfactant/budesonide and the pulmonary distribution following intra-tracheal administration
Published in Drug Delivery, 2019
Chung-Ming Chen, Chien-Hsiang Chang, Chih-Hua Chao, Mei-Hui Wang, Tsu-Fu Yeh
Radiosynthesis was done by using a commercial apparatus (TRACERlab FX F-N; GE Healthcare, USA), we dried aqueous 18 F-fluoride ion (∼10 mCi) by iterative cycles of addition and evaporation of acetonitrile, followed by complexation with K+-K2.2.2/K2CO3. The complex was then reacted with budesonide (10 mg) at 110 °C for 10 min in anhydrous dimethyl fluoride (0.6 ml), passed through a Sep-Pak C-18 to remove the free 18 F ion and followed by hydrolysis with NaOMe/methanol (1.0 ml). The specific radioactivity is 30 µCi/mg or greater. The radiolabelled products were analyzed with radio-HPLC and radio-thin-layer chromatography (radio-TLC). The results of radio-HPLC method were used for comparison and confirmation of that of radio-TLC. The radiochemical purity, determined by thin-layer chromatography, needs to be greater than 98%.
Effect of molecular size on interstitial pharmacokinetics and tissue catabolism of antibodies
Published in mAbs, 2022
Hanine Rafidi, Sharmila Rajan, Konnie Urban, Whitney Shatz-Binder, Keliana Hui, Gregory Z. Ferl, Amrita V. Kamath, C. Andrew Boswell
Radiosynthesis of 111In-labeled proteins was achieved through incubation of 111InCl3 and DOTA-conjugated (randomly through lysines) proteins in 0.3 mol/L ammonium acetate pH 7 at 37°C for 1 h. Radiosynthesis of 125I-labeled proteins was achieved through indirect iodination through tyrosine residues.69 Purification of all radioimmunoconjugates was achieved using NAP-5 columns equilibrated in PBS and confirmed by size-exclusion chromatography (Supplemental Figure S2).