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Highlights: • Focus is on the separation of Sr from Rb, Se and other metallic impurities such as Fe, Cr, and Ni cladding materials. • SNT and CST considered as an alternative to Chelex-100 for purification of 82Sr from bulk RbCl. • CST is suitable as a material in a cleanup column for removal of Se and Rb with capacity for Rb = 0.88 meq/g. • Uptake of Sr and Rb by SNT and Chelex-100 follows pseudo-second order kinetics. The 82Sr/82Rb generator system has found use in positron emission tomography (PET) imaging of myocardial perfusion. 82Sr is produced by proton irradiation of Rb metal/RbCl salt followed by chemical separation. Inorganic ion-exchangers were synthesized by hydrothermal methods and evaluated for the purification of accelerator-produced 82Sr from a RbCl target and co-produced impurities like 75Se, Fe, Cr, and Ni. A process consisting of removal of bulk RbCl using sodium nonatitanate (SNT), then removal of remaining tracers of Rb and Se using poorly crystalline silicotitanate (pCST) is suitable for 82Sr separation and achieves higher purity of 82Sr vs. commonly used organic resins. [ABSTRACT FROM AUTHOR]

Germanium-68 (Ge-68) is produced by proton irradiation of a gallium metal target and purified by organic extraction. The Ge-68 can be used in a medical isotope generator to produce Gallium-68 (Ga-68) which can be used to radiolabel PET imaging agents. The emerging use of Ge-68 in the Ga-68 medical isotope generator has caused us to develop a new purification method for Ge-68 that does not use toxic solvents. The purpose of this work was to develop a production scale separation of Ge-68 that utilizes a leaching step to remove a bulk of the gallium metal, followed by purification with Sephadex© G25. Production scale (300 mCi) purification was performed with the new method. The purified Ge-68 contained the highest radioactivity concentration of Ge-68 produced at BNL; the sample meet Department of Energy specifications and the method had an excellent recovery of Ge-68. [ABSTRACT FROM AUTHOR]

Abstract: Three 1,4,7,10-tetraazacyclododecane-N,N′,Nʺ,Nʺ′-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with 111In, 90Y and 177Lu and conjugated to the monoclonal antibody B72.3. The DOTA analogues evaluated were “NHS-DOTA” [N-hydroxysuccinimdyl (NHS) group activating one carboxylate], “Arm-DOTA” (also known as MeO-DOTA; with a p-NCS, o-MeO-benzyl moiety on the methylene group of one acetic acid arm) and “Back-DOTA” (with a p-NCS-benzyl moiety on a backbone methylene group of the macrocycle). The B72.3 was conjugated to the DOTA analogues to increase the retention time of the radioloabeled conjugates in vivo in mice. The serum stability of the various radiometalated DOTA conjugates showed them to have good stability out to 168 h (all >95% except 111In-NHS-DOTA-B72.3, which was 91% stable). Hydroxyapatite stability for the 111In and 177Lu DOTA-conjugates was >95% at 168 h, while the 90Y DOTA-conjugates were somewhat less stable (between 90% and 95% at 168 h). The biodistribution studies of the radiometalated DOTA-conjugates showed that no significant differences were observed for the 111In and 177Lu analogues; however, the 90Y analogues showed lower stabilities, as evidenced by their increased bone uptake relative to the other two [2–20% injected dose per gram (% ID/g) for 90Y and 2–8% ID/g for 111In and 177Lu]. The lower stability of the 90Y analogues could be due to the higher beta energy of 90Y and/or to the larger ionic radius of Y3+. Based on the bone uptake observed, the 177Lu-NHS-DOTA-B72.3 had slightly lower stability than the 177Lu-Arm-DOTA-B72.3 and 177Lu-Back-DOTA-B72.3, but not significantly at all time points. For 90Y, the analogue showing the lowest stability based on bone uptake was 90Y-Arm-DOTA-B72.3, perhaps because of the metal''s larger ionic radius and potential steric interactions minimizing effective complexation. The 111In analogues all showed similar biological distributions at the various time points. This study suggests that care must be taken when evaluating 90Y-labeled antibodies and in using NHS-DOTA-antibody conjugates with 177Lu. All evaluations should be extended to time points relevant to the half-life of the radiometal and the therapy applications. [Copyright &y& Elsevier]

Actinium-225 (225Ac) can be produced from a Thorium-229/Radium-225 (229Th/225Ra) generator, from high/low energy proton irradiated natural Thorium or Radium-226 target. Titanium based ion exchanger were evaluated for purification of 225Ac. Poorly crystalline silicotitanate (PCST) ion exchanger had high selectivity for Ba, Ag and Th. 225Ac was received with trace amounts of 227Ac, 227Th and 223Ra, and the solution was used to evaluate the retention of the isotopes on PCST ion exchanger. Over 90% of the 225Ac was recovered from PCST, and the radiopurity was >99% (calculated based on 225Ac, 227Th, and 223Ra). The capacity of the PCST inorganic ion exchange for Barium and 232Th was determined to be 24.19 mg/mL for Barium and 5.05 mg/mL for Thorium. PCST ion exchanger could separate 225Ac from isotopes of Ra and Th, and the process represents an interesting one step separation that could be used in an 225Ac generator from 225Ra and/or 229Th. Capacity studies indicated PCST could be used to separate 225Ac produced on small 226Ra targets (0.3–1 g), but PCST did not have a high enough capacity for production scale Th targets (50–100 g). [ABSTRACT FROM AUTHOR]

During the purification of radioisotopes, decay periods or time dependent purification steps may be required to achieve a certain level of radiopurity in the final product. Actinum-225 (Ac-225), Silver-111 (Ag-111), Astatine-211 (At-211), Ruthenium-105 (Ru-105), and Rhodium-105 (Rh-105) are produced in a high energy proton irradiated thorium target. Experimentally measured cross sections, along with MCNP6-generated cross sections, were used to determine the quantities of Ac-225, Ag-111, At-211, Ru-105, Rh-105, and other co-produced radioactive impurities produced in a proton irradiated thorium target at Brookhaven Linac Isotope Producer (BLIP). Ac-225 and Ag-111 can be produced with high radiopurity by the proton irradiation of a thorium target at BLIP.

Background: Radioimmunotherapy utilize a targeting antibody coupled to a therapeutic isotope to target and treat a tumor or disease. In this study we examine the synthesis and cell binding of a polymer scaffold containing a radiotherapeutic isotope and a targeting antibody., Methods: The multistep synthesis of a fluorescent or 149 Promethium-labeled Trastuzumab-polyethyleneimine (PEI), Trastuzumab, or PEI is described. In vitro uptake, internalization and/or the binding affinity to the Her2/neu expressing human breast adenocarcinoma SKBr3 cells was investigated with the labeled compounds., Results: Fluorescent-labeled Trastuzumab-PEI was internalized more into cells at 2 and 18 h than fluorescent-labeled Trastuzumab or PEI. The fluorescent-labeled Trastuzumab was concentrated on the cell surface at 2 and 18 h and the labeled PEI had minimal uptake. DOTA-PEI was prepared and contained an average of 16 chelates per PEI; the compound was radio-labeled with 149 Promethium and conjugated to Trastuzumab. The purified 149 Pm-DOTA-PEI-Trastuzumab had a radiochemical purity of 96.7% and a specific activity of 0.118 TBq/g. The compound demonstrated a dissociation constant for the Her2/neu receptor of 20.30 ± 6.91 nM., Conclusion: The results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed.

Eight halogenated N,N '-diphenethylethylenediamines were synthesized, characterized and evaluated for σ 1 receptor binding affinity in vitro. Measurements of lipophilicity also were obtained. The substitution pattern on one of the aromatic rings remained constant as 3,4-dichloro, while the substituents on the other aromatic ring were varied to include fluorine, bromine or iodine in either the 2-, 3- or 4- positions. Two main structure activity relationships were observed. First, halogen substitution on the 3- or 4-positions of the aromatic ring conferred higher binding affinities ( K i values 6.35 - 15.82 nM) than the corresponding substitutions at the 2-position ( K i values 12.08 - 43.15 nM). Second, derivatives containing either a bromo or fluoro substituent at a given position showed higher σ 1 receptor binding affinities than derivatives with a corresponding iodo substituent. The data indicate that σ 1 receptor affinity for this structural series is sensitive to steric bulk at the 2-position. Log k ' w measurements for the halogenated N,N '-diphenethylethylenediamines were determined by high performance liquid chromatography, and varied from 2.54 - 3.71. In particular, the 3-fluoro analog exhibited a log k ' w = 2.54 accompanied by a σ 1 receptor K i = 7.8 nM. These novel N,N'-diphenethylethylenediamines warrant further investigation in behavioral assays, and radiolabeled versions may prove suitable for in vivo studies of σ 1 receptors.