Radiochemical separation of 224Ra from 232U and 228Th sources for 224Ra/212Pb/212Bi generator.

The application of diagnostic and therapeutic radionuclides in nuclear medicine has grown significantly and has translated into the increased interest in radionuclide generators and their development. 224Ra and its shorter-lived daughters, 212Pb and 212Bi, are very interesting radionuclides from Targeted Alpha Therapy point of view for treatment of small cancers or metastatic forms. The purpose of the present work was to develop a simple generator for rapid elution of carrier-free 224Ra from 232U or 228Th sources by radiochemical separation based on extraction chromatography with the utilization of a home-made material. The bis(2-ethylhexyl) hydrogen phosphate (HDEHP) extractant was immobilized on polytetrafluroethylene (PTFE) grains and its ability to selectively adsorb 232U and 228Th, with simultaneous high elution recovery of 224Ra, was checked over few years. The 224Ra was quantitatively eluted with small volume (3-5 mL) of 0.1 M HNO3 with low breakthrough (<0.005%) and was used for further milking of 212Bi and 212Pb from DOWEX 50WX12 by 0.75 M and 2.0 M HCl, respectively. The elaborated here methods allowed high recovery of 224Ra, 212Pb and 212Bi radionuclides and their application in radiolabeling of various biomolecules.

Incorporation of no-carrier added 200,203Pb and 200,201,202Tl in calcium alginate and hesperidin incorporated calcium alginate beads.

When radioisotopes are injected to human body, instantly free radicals are generated due to the interaction of ionizing radiation with water and fluids present in the body. The vehicle carrying radionuclides into human body should therefore be designed in a way which could also eliminate or reduce such possibilities. For the first time we have used free radical scavenger hesperidin, a polyphenolic compound having a benzo-γ-pyrone with a benzene ring moiety for extraction of no-carrier added (NCA) 200,203Pb and 200,201,202Tl. We have modified CA beads by incorporation of a polyphenol (hesperidin) (CA-Hes). This tailor made beads were characterized and tested for their efficacy towards extraction of no-carrier-added lead and thallium radioisotopes from 40MeV α particle irradiated Hg2Cl2 target.

Automated cassette-based production of high specific activity [203/212Pb]peptide-based theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer.

A method for preparation of Pb-212 and Pb-203 labeled chelator-modified peptide-based radiopharmaceuticals for cancer imaging and radionuclide therapy has been developed and adapted for automated clinical production. Pre-concentration and isolation of radioactive Pb2+ from interfering metals in dilute hydrochloric acid was optimized using a commercially-available Pb-specific chromatography resin packed in disposable plastic columns. The pre-concentrated radioactive Pb2+ is eluted in NaOAc buffer directly to the reaction vessel containing chelator-modified peptides. Radiolabeling was found to proceed efficiently at 85°C (45min; pH 5.5). The specific activity of radiolabeled conjugates was optimized by separation of radiolabeled conjugates from unlabeled peptide via HPLC. Preservation of bioactivity was confirmed by in vivo biodistribution of Pb-203 and Pb-212 labeled peptides in melanoma-tumor-bearing mice. The approach has been found to be robustly adaptable to automation and a cassette-based fluid-handling system (Modular Lab Pharm Tracer) has been customized for clinical radiopharmaceutical production. Our findings demonstrate that the Pb-203/Pb-212 combination is a promising elementally-matched radionuclide pair for image-guided radionuclide therapy for melanoma, neuroendocrine tumors, and potentially other cancers.

Production and in vivo imaging of (203)Pb as a surrogate isotope for in vivo (212)Pb internal absorbed dose studies.

(212)Pb is a clinically relevant therapeutic alpha emitter isotope. A surrogate, (203)Pb, if prepared with sufficiently high specific activity could be used to estimate (212)Pb in vivo absorbed doses. An improved production procedure of (203)Pb with a simple, new separation method and high specific radioactivity for imaging is reported. We determined the in-vivo biodistribution of (203)Pb in mice by SPECT/CT. This highlights application possibilities of (203)Pb for further in vivo and clinical uses (radiolabeled (212)Pb-peptide co-injection, dosimetry calculation).

Purification of cyclotron-produced 203Pb for labeling Herceptin.

A simple and rapid procedure was developed for the purification of cyclotron-produced 203Pb via the 203Tl(d,2n) 203Pb reaction. A Pb(II) selective ion-exchange resin, with commercial name Pb Resin from Eichrom Technologies, Inc., was used to purify 203Pb from the cyclotron-irradiated Tl target with excellent recovery of the enriched Tl target material. The purified 203Pb was used to radiolabel the monoclonal antibody Herceptin. The in vitro and in vivo properties of the 203Pb radioimmunoconjugate were evaluated.

Validation of the integrity of a HEPA filter system.

The objective of this study was to establish a delayed air sampling method to verify the integrity of an existing HEPA filter system in a ventilated fume hood. (238U,232Th)O2 microspheres were generated to fabricate cement nuclear fuel pellets in a HEPA-filtered hood. To comply with the air effluent concentration limits by NRC, the capture efficiency of the HEPA filter was examined. An in-line isokinetic air sampling system was installed downstream of the HEPA filter. Utilizing a gas flow proportional counter, 212Pb was used as a surrogate to indicate any possible penetration of the (238U,232Th)O2 particles through the HEPA filter. Based on the experimental results, this delayed sampling method proved to be an easy and effective way to validate the integrity of the HEPA filter.

A 212Pb generator based on a 228Th source.

A two-compartment 212Pb generator has been constructed and characterized physically and chemically. It is based on transport by airflow of gaseous 220Rn emanating from thin layers of [228Th]barium stearate. 220Rn is collected in a glass bubbler by extraction into an organic solvent and solidified at temperatures below -72 degrees C. Tracer studies show that the decay product 212Pb can be recovered with approximately 70% yield. It is suggested that this generator design could accommodate therapeutic levels of 212Pb/228Th.

Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi generator: development of new methods, quantitative characterization, and implications for clinical use.

Bisumth-213, a short-lived alpha particle emitting radionuclide, is generated from the decay of 225Ac, which has a half-life of 10 days. The development of a clinical 225Ac/213Bi generator and the preparation of a 213Bi radiolabeled antibody for radioimmunotherapy of leukemia have been reported. The 225Ac decay scheme is complex; therefore a thorough understanding of the impact of both the parent 225Ac and its daughters on radiolabeling, purification, and quantification is necessary for optimal use of the generator system. This paper reports: (i) unique new methods to measure 221Fr, 213Bi, and 209Pb, the prominent daughters of 225Ac; and (ii) a quantitative evaluation of 225Ac/213Bi generator breakthrough and the radionuclidic purity of 213Bi labeled radiopharmaceutical dose formulations. A quantitative multi-dimensional proportional scanning method was employed to distinguish and measure specific daughter radionuclides. This method combines thin layer chromatography in two perpendicular directions with attenuated collimation as a function of time for data collection and analysis. Francium-221 and 213Bi eluted differentially from the generator, and 221Fr contributed minimally to unchelated 213Bi in the reaction and final products. Lead-209 was present in the reaction solution, but not strongly bound by the chelating moiety either (i) under the 213Bi labeling reaction conditions or (ii) following chelated 213Bi decay. As a consequence of incorporating several new procedures to the operation of the generator, 225Ac breakthrough in the final product was further reduced and represented a trivial contaminant in the final drug formulations.

Alpha spectrometry for measuring activity of glass-embedded 210PO isotope.

Measurements of exposure to radon are performed using numerous research methods which register either temporary or periodic radon concentrations. At the end of the 1990s reports on the possibility of defining past exposure to radon on the basis of measurement of the contents of 210Pb embedded in surface layer of glass were published. The registration of alpha particles emitted with glass was made using the spectrometric system. Use of the system for alpha spectroscopy leads finally to a significant lowering of the bottom threshold of detection and limits the influence of the negative background on the examined glass.

A new method for stable lead isotope extraction from seawater.

A new technique for stable lead (Pb) isotope extraction from seawater is established using Toyopearl AF-Chelate 650M(®) resin (Tosoh Bioscience LLC). This new method is advantageous because it is semi-automated and relatively fast; in addition it introduces a relatively low blank by minimizing the volume of chemicals used in the extraction. Subsequent analyses by HR ICP-MS have a good relative external precision (2σ) of 3.5‰ for (206)Pb/(207)Pb, while analyses by MC-ICP-MS have a better relative external precision of 0.6‰. However, Pb sample concentrations limit MC-ICP-MS analyses to (206)Pb, (207)Pb, and (208)Pb. The method was validated by processing the common Pb isotope reference material NIST SRM-981 and several GEOTRACES intercalibration samples, followed by analyses by HR ICP-MS, all of which showed good agreement with previously reported values.