Jonathan Fitzsimmons

Large scale accelerator production of 225Ac: Effective cross sections for 78–192 MeV protons incident on 232Th targets

Actinium-225 and 213Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of 225Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of 225Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL). Excitation functions for actinium and thorium isotopes, as well as for some of the fission products, are presented. The cross sections for production of 225Ac range from 3.6 to 16.7mb in the incident proton energy range of 78-192MeV. Based on these data, production of curie quantities of 225Ac is possible by irradiating a 5.0gcm-2 232Th target for 10 days in either BNL or LANL proton irradiation facilities.

Development of a production scale purification of Ge-68 from irradiated gallium metal

Abstract 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.

Production scale purification of Ge-68 and Zn-65 from irradiated gallium metal

Germanium-68 (Ge-68) is produced by proton irradiation of a gallium metal target, purified by organic extraction and used in a medical isotope generator to produce Gallium-68 PET imaging agents. The purpose of this work was to implement a production scale separation of Ge-68 and Zn-65 that does not use organic solvents and uses a limited number of columns. The current separation approach was modified to use AG1 resin and/or Sephadex(©) G25 with zinc spikes to purify Ge-68 with near quantitative recovery. The purified Ge-68 meets DOE specifications. Methods utilizing zinc spikes resulted in the purist Ge-68 produced at Brookhaven National Lab with no other impurities by ICP-OES. During process optimization approximately 2.5 Ci of Ge-68 was purified utilizing the different processing methods, and the material was sold to the Nuclear Medicine community between 2012-2013.

Synthesis and preliminary biological evaluations of fluorescent or 149Promethium labeled Trastuzumab-polyethylenimine

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 149Promethium-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 149Promethium and conjugated to Trastuzumab. The purified 149Pm-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.

Specific activity and isotope abundances of strontium in purified strontium-82

A linear accelerator was used to irradiate a rubidium chloride target with protons to produce strontium-82 (Sr-82), and the Sr-82 was purified by ion exchange chromatography. The amount of strontium associated with the purified Sr-82 was determined by either: ICP-OES or method B which consisted of a summation of strontium quantified by gamma spectroscopy and ICP-MS. The summation method agreed within 10% to the ICP-OES for the total mass of strontium and the subsequent specific activities were determined to be 0.25–0.52 TBq mg−1. Method B was used to determine the isotope abundances by weight% of the purified Sr-82, and the abundances were: Sr-82 (10–20.7%), Sr-83 (0–0.05%), Sr-84 (35–48.5%), Sr-85 (16–25%), Sr-86 (12.5–23%), Sr-87 (0%), and Sr-88 (0–10%). The purified strontium contained mass amounts of Sr-82, Sr-84, Sr-85, Sr-86, and Sr-88 in abundances not associated with natural abundance, and 90% of the strontium was produced by the proton irradiation. A comparison of ICP-OES and method B for the analysis of Sr-82 indicated analysis by ICP-OES would be easier to determine total mass of strontium and comply with regulatory requirements. An ICP-OES analytical method for Sr-82 analysis was established and validated according to regulatory guidelines.

Evaluation of Materials for the Separation of Germanium from Gallium, Zinc and Cobalt

In the past 68 Ge (Germanium-68) was purified with toxic organic solvents in liquid-liquid extractions making the product unacceptable by the FDA (food and drug Administration) for human use. The authors report initial studies utilizing three or four columns consisting of sequences of AG1, AG50, Chelex 100 and/or Sephadex G25 resins. Five purification methods were examined and a separation consisting of the sequence: AG1-Chelex100-Sephedex G25 provided 87% recovery of germanium. Fractionation of the elution resulted in high germanium concentrations.

Evaluation of SynPhase Lanterns for capturing Ac-225 from bulk thorium

Proton irradiation of a thorium (Th) target can produce Actinium-225 (Ac-225), but the irradiated thorium fissions results in the production of 100’s of other isotopes. SynPhase Lanterns containing sulfonic acid groups were evaluated for the purification of Ac-225 from Th and other fission metals. The SynPhase Lanterns were able to quantitatively and selectively capture Ac-225 and lanthanum (La) over Th. A second purification step would be needed to purify Ac-225 from trace amounts of Th and other fission products. The results from these studies were compared to similar studies performed with cation exchange resins, and the resins were superior at removing impurities.