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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.)

Introduction: The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality 76 Br, 77 Br, and 80m Br. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel 77 Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein., Methods: 76 Br, 77 Br, and 80m Br were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched Co 76 Se, Co 77 Se, and Co 80 Se intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The 77 Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination., Results: Cyclotron production yields were 103 ± 10 MBq∙μA -1 ∙h -1 for 76 Br, 88 ± 10 MBq∙μA -1 ∙h -1 for 80m Br at 16 MeV and 17 ± 1 MBq∙μA -1 ∙h -1 for 77 Br at 13 MeV. Radiobromide isolation yields were 76 ± 11% in a small volume of aqueous solution. The synthesized 77 Br-labeled PARP-1 inhibitor had a measured apparent molar activity up to 700 GBq/μmol at end of synthesis., Conclusions: A novel selenium alloy target enabled clinical-scale production of 76 Br, 77 Br, and 80m Br with high apparent molar activities, which was used to for the production of a new 77 Br-labeled inhibitor of PARP-1., Advances in Knowledge: New methods for the cyclotron production and isolation of radiobromine improved the production capacity of 77 Br by a factor of three and 76 Br by a factor of six compared with previous methods., Implications for Patient Care: Preclinical translational research of 77 Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale 77 Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic Co 77 Se., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article exist., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Isotope harvesting is a promising new method to obtain isotopes for which there is no reliable continuous supply at present. To determine the possibility of obtaining radiochemically pure radioisotopes from an aqueous beam dump at a heavy-ion fragmentation facility, preliminary experiments were performed to chemically extract a copper isotope from a large mixture of projectile fragmentation products in an aqueous medium. In this work a 93 MeV/u secondary beam cocktail was collected in an aqueous beam stop at the National Superconducting Cyclotron Laboratory (NSCL) located on the Michigan State University (MSU) campus. The beam cocktail consisted of ∼2.9% (67)Cu in a large mixture of co-produced isotopes ranging in atomic number from ∼19 to 34. The chemical extraction of (67)Cu was achieved via a two-step process: primary extraction using a divalent metal chelation disk followed by anion-exchange chromatography. A significant fraction (74 ± 4%) of the (67)Cu collected in the aqueous beam stop was recovered with >99% radiochemical purity. To illustrate the utility of this product, the purified (67)Cu material was then used to radiolabel an anti-EGFR antibody, Panitumumab, and injected into mice bearing colon cancer xenografts. The tumor uptake at 5 days postinjection was found to be 12.5 ± 0.7% which was in very good agreement with previously reported studies with this radiolabeled antibody. The present results demonstrate that harvesting isotopes from a heavy-ion fragmentation facility could be a promising new method for obtaining high-quality isotopes that are not currently available by traditional methods.

A proof of concept study was undertaken where non-carrier added (186 g)Re was produced from the cyclotron bombardment of (186)WC. (186)WC was carbo-thermally generated from a novel precursor synthesized from (186)WO3, aqueous ammonia and hexamethyltetramine. The inherent high electrical and thermal conductivity of this material, coupled with its high melting point, made it an ideal candidate for proton bombardment for production of (186)Re. An18 μA irradiation for 3h and processing via thermo-chromatography, (186)WC yielded 0.93 mCi of (186 g)Re which corresponds to 89% of the calculated theoretical yields. The radiochemical purity of the desired (186 g)Re species was found to be between 95 and 97% with small contaminants of (186)ReO2. The radiochemistry utility of the product was investigated using S-benzoyl-MAG3, and 100% complexation was achieved with stability being maintained for 96 h. The re-oxidation of (186)WC back to(186)WO3 by oxygen in the thermo-chromatography method of processing ensured that the starting material was regenerated and recovered from the process in 94-98% yield., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/μmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/μg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers' uptake in the liver by sixfold at 24 hours with ~ 1% ID/g and at 48 hours with ~ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ~ 0.7% ID/g and sevenfold at 48 hours with ~ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases.

An investigative study of the (100)Mo (p,2n)(99m)Tc reaction on a medical cyclotron using (100)Mo2C is reported. This is the first report of this compound being used as a target for this reaction. (100)Mo2C, a refractory carbide with high thermal conductivity, properties which underscore its use on a cyclotron, was synthesized using (100)MoO3. Its ease of oxidation back to (100)MoO3 under air at elevated temperatures facilitates the use of thermo-chromatography, a high temperature gas phase separation technique for the separation and isolation of (99m)Tc. Activity yields for (99m)Tc averaged 84% of the calculated theoretical yields. Additionally, the percent recovery of MoO3, the precursor for Mo2C, was consistently high at 85% ensuring a good life cycle for this target material. The produced (99m)Tc was radio-chemically pure and easily labeled MDP for imaging purposes., (© 2013.)

Halogen radioisotopes have a variety of physical half-lives which are suitable for probing a wide variety of pharmacokinetic processes. Compared with other radiohalogens, relatively little work has been done with radiochlorine. However, high specific activity radioisotopes of chlorine are available from low energy cyclotron production in quantities suitable for positron emission tomography (PET) and fundamental research. In particular, the sole radioisotope of chlorine which may be used for PET imaging, 34mCl, has achieved a state of development that permits imaging in clinical settings though sparse research effort has been focused on this isotope over the last 40 years. Additionally, the other longer-lived radioisotopes of chlorine will likely continue to show utility for more traditional radiotracer studies and chemistry development. [ABSTRACT FROM AUTHOR]

This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/mmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/mg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers' uptake in the liver by sixfold at 24 hours with ~ 1%ID/g and at 48 hours with ~ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ~ 0.7% ID/g and sevenfold at 48 hours with ~ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases. [ABSTRACT FROM AUTHOR]

89Zr has emerged as a useful radioisotope for targeted molecular imaging via positron emission tomography (PET) in both animal models and humans. This isotope is particularly attractive for cancer research because its half-life (t1/2 = 3.27 days) is well-suited for in vivo targeting of macromolecules and nanoparticles to cell surface antigens expressed by cancer cells. Furthermore, 89Zr emits a low-energy positron (Eβ+,mean = 0.40 MeV), which is favorable for high spatial resolution in PET, with an adequate branching ratio for positron emission (BR = 23%). The demand for 89Zr for research purposes is increasing; however, 89Zr also emits significant gamma radiation (Γ15 keV = 6.6 R⋅cm² /mCi⋅h), which makes producing large amounts of this isotope by hand unrealistic from a radiation safety standpoint. Fortunately, a straightforward method exists for production of 89Zr by bombarding a natural Y target in a biomedical cyclotron and then separation of 89Zr from the target material by column chromatography. The chemical separation in this method lends itself to remote processing using an automated module placed inside a hot cell. In this work, we have designed, built and commissioned a module that has performed the chemical separation of 89Zr safely and routinely, at activities in excess of 50 mCi, with radionuclidic purity > 99.9% and satisfactory effective specific activity (ESA). [ABSTRACT FROM AUTHOR]

The production of positron-emitting isotopes of manganese is potentially important for developing contrast agents for dual-modality positron emission tomography and magnetic resonance (PET/MR) imaging, as well as for in vivo imaging of the biodistribution and toxicity of manganese. The decay properties of 52 Mn make it an excellent candidate for these applications, and it can easily be produced by bombardment of a chromium target with protons or deuterons from a low-energy biomedical cyclotron. Several parameters that are essential to this mode of production—target thickness, beam energy, beam current, and bombardment time—depend heavily on the availability of reliable, reproducible cross-section data. This work contributes to the routine production of 52g Mn for biomedical research by contributing experimental cross-sections for natural chromium ( nat Cr) targets for the nat Cr( p , x ) 52g Mn reaction, as well as for the production of the radiocontaminants 52m,54 Mn. [ABSTRACT FROM AUTHOR]

Manganese-52g, 54 and Chromium-51 production cross-section measurements were conducted using natural chromium foils and copper monitor foils. Proton beam energies between 10 and 20 MeV were used for target bombardment. After bombardment, the irradiated foils were allowed to decay for at least 48 h and radioactivity was quantified using a high-purity germanium detector. The maximum 52gMn cross-section was 90.8 ± 16.0 mb at 14.3 ± 0.8 MeV. These data contribute to the existing nuclear data for cyclotron production of 52gMn at low to medium proton energies. • Investigating the cyclotron production of 52gMn using a proton beam. • Using Cu monitor reactions for the determination of energy. • Measuring the cross-sections of 52g,54Mn and 51Cr over an energy range of 10–20 MeV. [ABSTRACT FROM AUTHOR]

This work focused on the production and purification of the positron emitter 52Mn (t 1/2 = 5.6 d) via the natCr(p,n)52Mn reaction, using a TR24 cyclotron and a semi-automated system for the purification of 52Mn. Based on two-column and three-column systems, the recovery of 52Mn was 79.7 ± 6.2% (n = 3) and 70.8 ± 3.3% (n = 3), with processing times of 6.9 ± 0.5 h and 8.2 ± 0.6 h, respectively. • 52Mn was produced via irradiation of Cr foils using a solid-target coin system. • A semi-automated module was designed, constructed and optimized for the purification of 52Mn. • ICP-MS was used for elemental analysis of the starting material, after each column and waste for purifications of 52Mn. • HPGe was utilized for the irradiated samples to verify a high purity product with 54Mn contaminants <0.25%. [ABSTRACT FROM AUTHOR]

Titanium-45 (t 1/2 = 3.08 h) is a radiometal with excellent nuclear characteristics, including a high positron branching ratio (85%) and low average positron energy (0.439 MeV), for the development of PET imaging agents. 45Ti was produced via the 45Sc(p,n)45Ti reaction on the University of Alabama at Birmingham TR24 cyclotron in GBq quantities. Optimized separation methods were developed and preliminary radiochemistry studies were also carried out. This work shows 45Ti is a promising radiometal for future studies. • 45Ti was produced via irradiation of Sc foil using a solid-target coin system. • Radionuclidically pure product at yields suitable for research were obtained. • An optimized separation method for the use of 45Ti was developed. • Complexation studies of 45Ti with deferoxamine were conducted. [ABSTRACT FROM AUTHOR]

As part of an effort to develop aqueous isotope harvesting techniques at radioactive beam facilities, 48V and a cocktail of primary- and secondary-beam ions created by the fragmentation reaction of a 160 MeV/nucleon 58Ni beam were stopped in an aqueous target cell. After collection, 48V was separated from the mixture of beam ions using cation-exchange chromatography. The extraction efficiency from the aqueous solution was (47.0 ± 2.5)%, and the isolated 48V had a radiochemical purity of 95.8%. This proof-of-concept work shows that aqueous isotope harvesting could provide significant quantities of rare isotopes which are currently unavailable at conventional facilities. • A selective method was developed to separate the multivalent element vanadium from a complex mixture of elements (Z ~ 1–28). • Vanadium-48 was produced via heavy-ion fragmentation of a 58Ni beam at the National Superconducting Cyclotron Laboratory. • The primary- and secondary-beam ions, including 48V, were stopped in an aqueous target cell and characterized. • By way of cation-exchange chromatography, the 48V recovery was 47.0 ± 2.5%. • The radionuclidic purity of the recovered 48V was 95.8 ± 2.5%. [ABSTRACT FROM AUTHOR]