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203 Pb is a surrogate imaging match for 212 Pb. This elementally matched pair is emerging as a suitable pair for imaging and targeted radionuclide therapy in cancer care. Because of the half-life (51.9 h) and low-energy γ-rays emitted, 203 Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity 203 Pb using electroplated thallium targets. We further investigated the radiochemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-α-NET (lead-specific chelator conjugated to tyr3-octreotide via a polyethylene glycol linker). Methods: Targets were prepared by electroplating of natural or enriched ( 205 Tl) thallium metal. Scanning electron microscopy was performed to determine the structure and elemental composition of electroplated targets. Targets were irradiated with 24-MeV protons with varying current and beam time to investigate target durability. 203 Pb was purified from the thallium target material using an extraction resin (lead resin) column followed by a second column using a weak cation-exchange resin to elute the lead isotope as [ 203 Pb]PbCl 2 Inductively coupled plasma mass spectrometry studies were used to further characterize the separation for trace metal contaminants. Radiolabeling efficiency was also investigated for DO3A chelator and VMT-α-NET (a peptide-based targeting conjugate). Results: Electroplated targets were prepared at a high plating density of 76-114 mg/cm 2 using a plating time of 5 h. A reproducible separation method was established with a final elution in HCl (400 μL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 ± 5.4 GBq/μmol (1.1 ± 0.1 Ci/μmol). Conclusion: An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine 203 Pb production with high recovery yields and purity., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4- 18 F-fluoro-3-[hydroxymethyl]butyl)guanine ([ 18 F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII- animal models, with more than 10-fold higher [ 18 F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug Administration-approved theranostic pair is the 68 Ga- and 177 Lu-labeled DOTATATE peptides, which are used to image neuroendocrine tumors, predict treatment response, and treat disease. However, when using radionuclides of 2 different elements, differences in the pharmacokinetic and pharmacodynamic profile of the agent can occur. Theranostic agents that incorporate the matched-pair radionuclides of scandium- 43 Sc/ 47 Sc or 44 Sc/ 47 Sc-would guarantee identical chemistries and pharmacologic profiles. The aim of this study was to investigate production of 43,44,47 Sc via proton-induced nuclear reactions on titanium nuclei using a 24-MeV cyclotron. Methods: Aluminum, niobium, and tantalum target holders were used with titanium foils and pressed TiO 2 to produce scandium radionuclides with proton energies of up to 24 MeV. Irradiated targets were digested using NH 4 HF 2 and HCl in a closed perfluoroalkoxy alkane vessel in 90 min. Scandium radionuclides were purified via ion-exchange chromatography using branched N,N,N',N' -tetra-2-ethylhexyldiglycolamide. The titanium target material was recovered via alkali precipitation with ammonia solution. Results: Titanium foil and TiO 2 were digested with an average efficiency of 98% ± 3% and 95% ± 1%, respectively. The typical digestion time was 45 min for titanium foil and 75 min for TiO 2 The average scandium recovery was 94% ± 3%, and the average titanium recoveries from digested titanium foil and TiO 2 after precipitation as TiO 2 were 108% ± 8% and 104% ± 5% of initial mass, respectively. Conclusion: This work demonstrated a robust method for the cyclotron production of scandium radionuclides that could be used with natural or enriched TiO 2 target material., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

15 O (half-life, 122 s) is a useful radionuclide for PET applications. Current production of 15 O typically makes use of the 14 N(d,n) 15 O, 15 N(p,n) 15 O, or 16 O(p,pn) 15 O reactions using an accelerator. A novel approach for the production of 15 O is via the 16 O(γ,n) 15 O reaction using an electron linear accelerator. Photonuclear reactions using an electron linear accelerator may allow for feasible and economical production of 15 O compared with the current methods. Methods: In this work, experiments using a repurposed Clinac were conducted using oxygen-containing alumina as a target material to study the production rate of 15 O. Additional studies were conducted using a water target cell. Simulations using Geant4 were conducted to predict the activity and power dissipation in the target. Results: Bremsstrahlung radiation from the electron beam, and consequently 15 O production via photonuclear reactions, is enhanced when a high- Z material, tungsten, is placed in front of the target. The alumina irradiations provided preliminary data to optimize the beam parameters and target configuration. The optimal thickness of tungsten was 1.4 mm for both the simulated and the measured studies of alumina. Simulations of irradiated water targets showed that tungsten thicker than 1.4 mm resulted in fewer photons available to activate the water; thus, a higher current was required to achieve a fixed dose. Alternatively, for a constant tungsten thickness, more power was deposited in the target with increasing beam energy, requiring a lower current to achieve a fixed dose. Actual irradiations of a water target yielded a quantity of 15 O in the water that was consistent with expectations based on irradiations of alumina. Conclusion: Several parameters should be considered regarding the photonuclear production of 15 O for an average patient dose of 1,850 MBq (50 mCi) in 10 mL. This work illustrates a variety of machine parameters capable of achieving a reasonable patient dose. Our simulations show that the power deposited in the target for these parameters is less than that in commercially operated cyclotron targets for the production of 18 F. Thus, this work demonstrates that the photonuclear production of 15 O may be a new production path for this useful radionuclide., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

With the increasing focus on a more personalized approach to medicine using imaging techniques to select patients for targeted treatment or theranostic strategies, interest in the development of new radionuclides is expanding. Through the development of production and radiochemistry techniques, several new radiometals are being added to the toolbox of the nuclear imaging community. 43,44g,m Sc, 52g Mn, and 45 Ti are all emerging transition metal radionuclides and will be discussed in this short review. Each of these nuclides has unique imaging characteristics and shows promise for the development of new molecular imaging agents., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)