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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
The radiopharmaceutical preparation is directly affected by the physical half-life. This includes the delivery of the radioisotope to the chemistry lab, radiosynthesis, purification, quality control, and the delivery of the radiolabeled product to the imaging lab. These processes need to be optimized particularly for the mostly rather short-lived PET radiotracers. But nuclear decay may also be significant in some 99mTc radiotracer preparations if, for example, the purification process and delivery to the imaging lab take hours. The radiochemist may be challenged to speed up the purification process or to devise a new radiosynthesis route to obtain an acceptable purity profile directly after synthesis. Finally, significant nuclear decay may reduce the radiochemical activity concentration (RAC) of the radiotracer preparation to a level below the requirements of an imaging study. In turn, the RAC at the end of synthesis may have to be increased leading to accelerated autoradiolysis. Again radiochemistry can provide a solution by adding a radiostabilizer to the formulation.
Separation of Radiogallium from Zinc Using Membrane-Based Liquid-Liquid Extraction in Flow: Experimental and COSMO-RS Studies
Published in Solvent Extraction and Ion Exchange, 2019
Kristina Søborg Pedersen, Karin Michaelsen Nielsen, Jesper Fonslet, Mikael Jensen, Fedor Zhuravlev
Radiogallium (66,67,68Ga = *Ga) has a long and notable history in nuclear medicine. For years, gallium-67 (67Ga, t1/2 = 78 h) scintigraphy has been a linchpin of molecular imaging of cancer,[1] including non-Hodgkin’s lymphoma, Hodgkin’s disease,[2] as well as various infections.[3] The advancement of positron emission tomography (PET) and FDA’s approval of [68Ga]Ga-DOTA-TATE (Netspot®) moved gallium-68 (68Ga, t1/2 = 68 min) to the forefront of neuroendocrine tumor diagnostics.[4] In recent years [68Ga]Ga-HBED-PSMA-11, a 68Ga-labeled PSMA (prostate-specific membrane antigen) ligand emerged as the gold standard for prostate cancer diagnostics, driving a high adoption rate of 68Ga in clinics.[5] The easy chelation chemistry and convenience of 68Ge/68Ga-generators further contribute to 68Ga popularity in clinical and pre-clinical settings.[6] Meeting the growing demand for 68Ga is a challenge, as it is mostly supplied by the gallium generators which suffer from high prices, long lead time, quality inconsistencies, and limited shelf life.[7] An alternative method of 68Ga production is the irradiation of 68Zn using a cyclotron.[8] Since many PET-centers have their own cyclotrons, this is potentially a convenient means of in-house production of 68Ga-tracers. However, the cyclotron production of 68Ga in solid targets from 68Zn and its subsequent separation require either installation of expensive automated solid target systems or requires a series of manual pre- and post-irradiation target handlings. Recently, the production of 68Ga in liquid targets from enriched 68Zn salt solutions has been described, using either [68Zn]ZnCl2[9,10] or [68Zn]Zn(NO3)2.[11–13] Compared to the solid target production, the solution target approach leads to lower radionuclide yields but has an advantage of being more amenable to automation. Currently, all 68Ga made in cyclotron solution targets is produced in batch mode; the desired radionuclide is subsequently purified from the 68Zn salt solution by solid-phase extraction (SPE) using commercial radiosynthesis modules, without directly recycling the 68Zn. If recycling of isotopically enriched 68Zn target material is desired, reprocessing needs to be performed in a separate step.