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Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added 55 Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with 55 Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [ 55 Co]CoCl 2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [ 55 Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [ 55 Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [ 55 Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [ 64 Cu]Cu-NT-Sarcage, [ 55 Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including 55 Co for PET and 58m Co for therapeutic applications.

The aim of this work was to explore 132 La as a PET imaging surrogate for 225 Ac using a DOTA-based, tumor-targeting alkylphosphocholine (NM600). Methods: 132 La was produced on a biomedical cyclotron. For in vivo experiments, mice bearing 4T1 tumors were administered 132 La-NM600, and PET/CT scans were acquired up to 24 h after injection. After the last time point, the ex vivo tissue distribution was measured to corroborate the in vivo PET data. The ex vivo tissue distribution in mice was determined at 4 and 24 h after injection of 225 Ac-NM600. Results: PET/CT images showed elevated, persistent 132 La-NM600 uptake in the tumor. Low bone accumulation confirmed the in vivo stability of the conjugate. Ex vivo biodistribution studies validated the image-derived quantitative data, and the comparison of the 132 La-NM600 and 225 Ac-NM600 tissue distributions revealed a similar biodistribution for the 2 radiotracers. Conclusion: These findings suggest that 132 La is a suitable imaging surrogate to probe the in vivo biodistribution of 225 Ac radiotherapeutics., (© 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.)

Abstract: Production of 38Cl and 34mCl via the (d, α) reaction on natural argon and 36Ar reveal medical cyclotrons’ ability to supply these isotopes in small quantities. 38Cl provides an inexpensive developmental tool, while 34mCl is a positron emitter of interest in PET imaging. Production yields, cyclotron target development, cryo-recovery of enriched gases, and nucleophilic chemistry of a model compound are described. [Copyright &y& Elsevier]

Background: Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide 177Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce 165Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho(m) targets to produce 165Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified 165Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [165Er]PSMA-617. Results: Irradiation of 80–180 mg natHo targets with 40 µA of 11–12.5 MeV protons produced 165Er at 20–30 MBq·µA−1·h−1. The 4.9 ± 0.7 h radiochemical isolation yielded 165Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/165Er separation factor of (2.8 ± 1.1) · 105. Radiolabeling experiments synthesized [165Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol−1. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale 165Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [165Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer. [ABSTRACT FROM AUTHOR]

We report an extraction chromatography-based method via Actinide Resin for the isolation of radio-manganese from both natural chromium and isotopically enriched iron targets for cyclotron production of 52gMn and 51Mn. For the separation of 52gMn from natCr, a decay-corrected radiochemical yield of 83.7 ± 8.4% was achieved. For 51Mn from 54Fe, a decay-corrected radiochemical yield of 78 ± 11% was achieved. This automatable method efficiently isolates both radionuclides from accelerator target material. [ABSTRACT FROM AUTHOR]

Abstract We report a novel, precipitation-based method for the isolation of Mn from Cr targets for cyclotron production of 52gMn. The separation produces no-carrier-added 52gMn with a decay corrected radiochemical yield of 85 ± 3% and apparent molar activity for DOTA of 1.3 GBq/μmol. This method reduces stable metallic impurities in the purified 52gMn compared to previously reported chromatographic methods. Highlights • Radiochemical separation using a 2-phase precipitation method and single extraction chromatography column. • Separation strategy for production no-carrier-added 52gMn. • Process allows for chelation studies with DOTA. [ABSTRACT FROM AUTHOR]

Cobalt-55 and -58m form a theranostic pair that has relevant properties for cancer research. We report a cation exchange chromatography/extraction chromatography method that separates cyclotron-produced 55/58mCo from 54/57Fe in <1.5 h, recovers >85% Co and achieves [55Co]Co-NOTA and -DOTA AMA 89 ± 48 and 35 ± 7 MBq/nmol (EOB), respectively. Cobalt-55 and -58m were quantitatively labeled to functionalized NOTA at 106 and 50 MBq/nmol (EOB), respectively, corroborating measured AMA. This method is faster than previously published methods and achieves better [55/58mCo]Co-NOTA and -DOTA AMA. • [55Co]Co-NOTA/DOTA apparent molar activity 89 ± 48/35 ± 7 MBq/nmol (N=6) at EOB. • 58mCo quantitatively labeled at 50 MBq/nmol to functionalized NOTA (EOB). • 55/58mCo separated from 54/57Fe via cation exchange and extraction chromatography in < 1.5 h. • >85% Co RCY in 1 mL and >99.99% 55Co radionuclidic purity. • >98% 54/57Fe recovery and resulting 54/57Fe can be electrodeposited. [ABSTRACT FROM AUTHOR]