Robert Nickles

Quantitative PET with positron emitters that emit prompt gamma rays

The purpose of this work was to determine the feasibility of using positron emitting isotopes that emit prompt gammas to acquire quantitative positron emission tomography (PET) data using standard PET instrumentation. Prompt gammas can contaminate PET data by increasing dead time, converting singles into invalid coincidences, and producing multiple coincidences which can lead to the replacement of valid coincidences by invalid coincidences. The measurements in this work were made by scanning point sources containing F-18, Na-22, and Co-60 and studying the effects of the prompt gammas on the PET data, We found that for the Na-22 point source, the annihilation photon coincidence rate was about 25 times the prompt gamma-annihilation photon coincidence rate in the entire active volume of the scanner. With scatter, the Na-22 prompt gamma-annihilation photon coincidence rate was 1.3 times higher than the F-18 scatter coincidence rate. The most significant effect of the prompt gamma was to increase dead time; the dead time correction factor for Cu-60 was 2.4 times higher than the correction factor for N-13 for the same source activity. We conclude that, in many cases, quantitative PET data can be readily obtained with isotopes that emit prompt gammas, using standard PET 2-D instrumentation. However there are some cases, such as 3-D PET, where prompt gammas could significantly contaminate the PET data.

Auger electron-based targeted radioimmunotherapy with 58mCo, a feasibility study

Co-58m (t1/2=9.10u2005h, 100% IC) is an attractive radionuclide for localized delivery of radiation dose due to its emission of Auger and conversion electrons with high LET in water (2-18 keV/µm). 58mCo decays to a positron-emitting daughter, 58gCo (t1/2=70.86 d, 14.9% β+), which can be readily detected by Positron Emission Tomography (PET) and hence can be employed to verify the biodistribution of the parent isotope post-treatment in vivo. In this work, we describe 1) the targetry and radiochemistry involved in the production of high specific activity 58mCo; and 2) the results of a pilot radiotherapy study using a 58mCo-labeled anti-CD105 antibody (TRC105) in a mouse model of mammary carcinoma. The presented methods allow for the production of 14.3±3.2 MBq/µAh of 58mCo with a separation efficiency of 96±2% and a specific activity with NOTA of 25±6 GBq/µmol. We have produced ∼640 MBq of 58mCo-NOTA-TRC105, with a specific activity of 1.2 MBq/µg, in 800u2005µL of PBS ready for targeted radioimmunotherapy, which we ...

Simplified and reproducible radiochemical separations for the production of high specific activity 61Cu, 64Cu, 86Y and 55Co

Four positron-emitting radiometals 61Cu, 64Cu, 86Y and 55Co are increasingly being employed as labels for positron emission tomography (PET) imaging due to their favorable half-lives that match the pharmacokinetics of targeting moeities such as peptides, antibodies and antibody fragments and due to their use in internal dosimetry and treatment planning of targeted radionuclide therapy when they are substituted by their therapeutic analogues 67Cu, 90Y and 58mCo. The main disadvantage of the production methods reported in the literature for these radionuclides is that the final separated radioactive product is diluted in a large volume (> 5u2005mL), which obligates a lengthy evaporation step in a large vessel that is difficult to automate in-line after the chromatographic steps and that results in a highly variable amount of radioactivity lost in the vessel’s surface. In this work we present simplified radiochemical separation methods for the production of 61Cu, 64Cu, 86Y and 55Co that result in: 1) a final elu...

Radiobromine production, isolation and radiosynthesis for the development of a novel prostate cancer radiotherapeutic agent

The radioactive isotopes of bromine accessible with low energy medical cyclotrons have unique potential for diagnostic and radiotherapeutic nuclear medicine applications. These include bromine-76 (t1/2 = 16u2005h) for positron emission tomography and bromine-77 (t1/2 = 57u2005h) for Auger radionuclide therapy. Methods are presented to synthesize NiSe discs from elemental starting materials for proton irradiation in a 4π water cooling target configuration. Radiobromide was isolated from the irradiated NiSe material by dry distillation and used to radiolabel 7α-BrDHT for investigation as an Androgen-receptor-targeted theranostic radiopharmaceutical.

Earth, air, fire and water: A targetry quartet

Cyclotron targets have made steady progress in terms of current capabilities, automated handling and application to isotopically-enriched material. These advances have followed a distinct trajectory at the University of Wisconsin, with the emphasis on maximizing the yield of the desired radionuclide within the strict constraints of heat transfer of beam power and the ultimate recycling of precious target stock. This approach leads to four target families, each employed in the production of the positron-emitting transition metals of the 3d- and 4d-subshells, with importance now arising as targeted molecular imaging agents.