Patrick M. Grant

THE PREPARATION OF A RUBIDIUM-82 RADIONUCLIDE GENERATOR

Abstract82Sr has now been produced by the spallation of Molybdenum by protons of up to 800 MeV. The radiochemical recovery of strontium is described together with a description of the analytical techniques used to estimate recovered yields of the various radionuclides generated. A radionuclide generator is described for the rapid recovery of82Rb, the 1.25 min half-life decay product of82Sr. An outline is given of the quality control procedure adopted to ensure that the82Rb is suitable for clinical use.

Medium-energy spallation cross sections. 1. RbBr irradiation with 800-MeV protons

Radiochemical and instrumental methods have been used to measure the production cross sections of 40 spallation products induced in RbBr targets by 800-MeV protons. RbBr is irradiated at LAMPF to produce the following isotopes for use in diagnostic nuclear medicine: 75Se—(67±2)mb; 72Se—(12±0.4)mb; 68Ge—(19±1)mb; 67Ga—(41±1)mb; 62Zn—(2±1)mb; 67Cu—(1.6±0.08)mb.

The production and recovery of 77Br at Los Alamos for nuclear medicine studies

Abstract A procedure for the synthesis and isolation of 77 Br for nuclear medicine research has been developed at LASL. Metallic Mo targets are irradiated at LAMPF with medium-energy protons at high beam current. Following dissolution, volatilization, precipitation, and ion exchange techniques, 77 Br is recovered with a (91±7)% chemical yield and is completely free of all other radioactive species with the exception of small levels of 76 Br and 82 Br. Ci-quantity production capabilities have been demonstrated, and the product is proving successful for the labelling of diverse radiopharmaceuticals. Future improvements in the process are also discussed.

The isolation of 82Sr from 200 to 600 MeV proton-irradiated Mo targets for biomedical applications

Abstract 82 Sr is of interest in nuclear medicine as the generator of its short-lived daughter, 82 Rb. Experimentation has begun at the Clinton P. Anderson Meson Physics Facility, and spallation reactions have been induced in Mo targets with 200–600 MeV protons to produce microcurie amounts of a variety of radionuclides. A six-step radiochemical procedure, incorporating precipitation, solvent extraction, and ion exchange techniques, has been developed for the separation and purification of Sr radioactivities from other spallation products and the bulk target material. γ-Ray spectrometry was used for isotope characterization, and chemical yields of ten different spallation-induced radioelements were determined for this analytical scheme. Radiostrontium can be quantitatively recovered in a sufficiently decontaminated state for use in biomedical generator development, and this procedure is being scaled up to a hot cell operation for actual production irradiations.

The production, recovery, and purification of 172Hf for utilization in nuclear medicine as the generator of 172Lu.

Abstract 172 Hf is of potential value in nuclear medicine research as the generator of its daughter nuclide, 172 Lu. The latter isotope, a heavy rare-earth tracer, could have applications in compound labelling, pre-clinical biodistribution studies, and other areas of investigation. 172 Hf is produced by inducing spallation reactions in Ta targets with medium-energy protons at LAMPF, and a chemical procedure has been developed for the separation of radiohafnium from the bulk target material and various spallogenic impurities. Nuclide identification was accomplished by gamma-ray spectrometry, and radiochemical yields of nine different elements in the analytical scheme were measured. 172 Hf is thus recovered quantitatively (93% chemical yield) and is sufficiently decontaminated for use in generator development.

Analysis of fission products using capillary electrophoresis with on-line radioactivity detection

Capillary electrophoresis has been used to separate metal ions characteristically associated with nuclear fission. Indirect UV absorbance and on-line radioactivity detection were used simultaneously to monitor the analytes. The radioactivity detector consists of conical plastic scintillating material with the capillary passing through the center to provide a 4π detection geometry. The wide end of the cone is optically coupled to a photomultiplier tube. Transient isotachophoretic techniques were employed to stack large volumes of samples which had low specific activities. Radioactivity detection of (152)Eu and (137)Cs was achieved at the nanocurie level for 80-100 nL injections. The detector is approximately 80% efficient, enabling samples resident in the detector window for 0.1 min to be reliably assayed. The separation of (137)Cs and (137m)Ba isotopes, which are in secular equilibrium, was modeled to demonstrate the effects of the rapid decay of (137m)Ba.

Pancuronium Bromide (Pavulon) Isolation and Identification in Aged Autopsy Tissues and Fluids

The isolation and detection of pancuronium bromide was developed for aged autopsy samples to identify and confirm this compound in questioned tissue samples. A novel protocol was optimized for the isolation of the target drug in highly decomposed tissues. Solid-phase extraction (SPE) cartridges containing styrene-divinylbenzene were investigated. This polymer retained quaternary drugs and facilitated sequential elution upon washing with commonly available solvents. The semi-purified SPE samples were prescreened by pyrolysis GC-MS. A candidate specimen was then confirmed by microbore high-performance liquid chromatography/electrospray-ionization/mass spectrometry (microHPLC-ESI-MS/MS) with a triple-quadrupole mass spectrometer. The developed procedures provided a qualitative or semiquantitative (at best) basis for the investigation of difficult cases involving overdoses of polar drugs.

Scope and limitations of a rapid radiobromination technique

A series of model compounds has been labeled with bromine-77 using a recently described method for rapid radiobromination. Characterization of the 77 Br-labeled products has shown the technique to be unsuitable for labeling fragile molecules, such as proteins. Thus, the technique should not be considered a generally applicable radiobromination method; however, it may be a useful means of attaching radiobromine to some simple molecules which are not sensitive to oxidative conditions and do not possess multiple sites for halogenation.

The application of pancuronium bromide (Pavulon) forensic analyses to tissue samples from an "Angel of Death" investigation.

The case report of a serial killer who worked at several hospitals as a respiratory therapist is presented. The suspect was initially labeled a benevolent Angel of Death who ended the suffering of elderly patients through mercy killing. However, his subsequently declared motive for homicide was very different from other similar cases in medical settings. The application of new analysis techniques for the detection of pancuronium bromide in a series of aged exhumation tissues gave positive results and led to the resultant conviction of the therapist.

Radioassay problems associated with the clinical use of a 82Rb radionuclide generator

The short-lived positron emitting radionuclide 82Rb (t1/2 1.27 min) is conveniently available from a 82Sr/82Rb generator system. The parent nuclide (t1/2 25.5d) produced from the spallation of molybdenum, has associated with it varying quantities of other long-lived strontium radionuclides, namely 85Sr, 89Sr and 90Sr. It is important therefore in the clinical use of such material that the levels of strontium radionuclides being administered to patients is carefully assayed and controlled. The problems associated with these measurements are discussed with special reference to the radiation dose received by the patient and the problems in resolving overlapping peaks with different FWHMs.