PubMed Health⌕ Search

Biomedical subjects

J Zweit

Publications and source records attributed to J Zweit.

27 records · Page 2Linked to original sources
PubMed1996

Radionuclides and carrier molecules for therapy.

Although radionuclide therapy has been around for a long time, this modality of cancer treatment has been limited mainly to the use of [32P]-phosphate and [131I]-sodium iodide. The last few years, however, have seen an increased interest in this area due to new developments of radionuclides and carrier molecules that may provide selective targeting of tumour sites. The potential of this technique can be further realized if the radionuclide is carefully selected to match both the localization of the carrier molecule and tumour morphology. This paper briefly reviews radionuclides in current use and potential candidates for targeted therapy. Decay characteristics, production methods and relevant chemical properties are discussed.

Humans↗
PubMed1994

Evaluation of copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) for tissue blood flow measurement using a trapped tracer model.

Copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62,64Cu is a promising radiotracer for the study of blood flow using positron emission tomography (PET). We have investigated the application of a simple trapped tracer model to measurements of tissue 64Cu-PTSM uptake combined with continuous arterial sampling. A dual-tracer method was used to compare blood flow estimated by 64Cu-PTSM with values derived from measurements using cobalt-57 microspheres in the rat. Prolonged retention of 64Cu-PTSM following intravenous administration was initially confirmed in both normal tissues and tumours. After intraventricular 64Cu-PTSM infusion, cumulative arterial 64Cu activity increased progressively, and after extraction in n-octanol was found to plateau to levels corresponding with those reached following administration of 57Co microspheres. Rapid and species-dependent rates of 64Cu-PTSM decomposition to non-extractable 64Cu complexes were found in rat and human blood in vitro (70% +/- 6% and 43 +/- 5% respectively at 16 min), demonstrating the need for immediate processing of arterial samples. Close agreement was found between blood flow estimated by 64Cu-PTSM and 57Co microsphere methods in tissues of low to moderate flow: muscle (0.01, 0.08, 0.07 ml/min per gram; mean difference, mean 64Cu, mean 57Co), brain (0.09, 0.52, 0.43 ml/min per gram) and kidney (-0.16, 2.29, 2.45 ml/min per gram). Estimates of cardiac output also compared favourably between the two methods (5.7, 59.8, 54.1 ml/min). We conclude that a simple tissue trapping model may be suitable for the derivation of blood flow estimates using 62,64Cu-PTSM, PET imaging and continuous arterial blood sampling.

Animals↗
PubMed1994

Nickel-57-doxorubicin, a potential radiotracer for pharmacokinetic studies using PET: production and radiolabelling.

The clinical use of anthracyclines, such as doxorubicin (DXR), is hampered by tumour development of multidrug resistance (MDR). The drug efflux associated with MDR could be characterised in vivo using Positron Emission Tomography (PET) in conjunction with a suitable radiolabelled drug. We are investigating DXR labelled with the positron emitter 57Ni as a potential analogue of the parent drug. Essential to this work is the production of a high purity radionuclide in a suitable chemical form for the preparation of radiolabelled DXR. To optimise production parameters, excitation functions (reaction cross section as a function of beam energy) for proton induced reactions in cobalt were measured up to 60 MeV. The excitation function for the 59Co(p,3n)57Ni reaction shows a maximum cross section of 13.8 +/- 1.5 mb at 38 MeV. The optimum energy range for production of 57Ni was found to be 41-->26 MeV resulting in an experimental thick target yield of 17.8 MBq/muAh. The level of the 56Ni impurity is only 0.21% at the end of bombardment. A radiochemical procedure, based on cation-exchange chromatography, has been developed for the separation of radionickel from the cobalt target and other radiochemical and chemical impurities. The 57Ni activity was eluted, using 2M HCl, from a Dowex-50Wx8(H+) column, in a 95% radiochemical yield. Optimum labelling of DXR has been investigated in terms of pH, reaction time and temperature, achieving radiochemical yields > 94%. DXR labelled with 57Ni therefore shows promise as a radiotracer for pharmacokinetic studies using PET.

Doxorubicin↗
PubMed1994

Tissue blood flow estimation with copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) and PET.

Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging the distribution of blood flow with positron emission tomography (PET). The application of a simple trapped tracer model in conjunction with tissue uptake and continuous arterial sampling to estimate blood flow has been compared with the 57Co-microsphere method in the rat. After intraventricular injection the cumulative arterial function for 64Cu increased progressively due to the presence of circulating non lipophilic complexes. The cumulative function for lipophilic 64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those reached by 57Co-microspheres. No consistent disagreement was found between cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean), brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55 mL/min/g). A simple tissue trapping model may therefore be suitable for the derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu-PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.

Animals↗
PubMed1992

Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography.

Clinical utilisation of positron emission tomography could be enhanced by the availability of short-lived radionuclides derived from generator systems. The zinc-62/copper-62 combination is one such system which could be used as a source for a number of copper-62 radiopharmaceuticals. We have developed and optimised a high activity (5.6 GBq, 150 mCi) zinc-62/copper-62 generator to provide 62Cu in a form that is suitable for direct labelling of pyruvaldehyde-bis-(N4-methylthiosemicarbazone)-copper(II), Cu(PTSM). The distribution coefficients of Zn(II) and Cu(II) between anion-exchange resin and various hydrochloric acid/organic solvent mixtures were measured. Based on these measurements a generator eluent of 0.3 M HCl/40% ethanol provided 62Cu in greater than 90% yield in a 3-ml volume. A very low 62Zn breakthrough of less than 3 x 10(-7)% was achieved. Copper-PTSM was successfully labelled with the no-carrier-added 62Cu eluent directly from the generator with 94% radiochemical yield.

Copper↗
PubMed1988

A method for the production of iron-52 with a very low iron-55 contamination.

The production and radiochemical separation of 52Fe from 4He irradiation of enriched 50Cr target is described. Methods developed for the recovery of the target material (50Cr) are also described. The yield of 52Fe at 38 MeV incident 4He energy is 1667 +/- 133 MBq/C (163 +/- 13 microCi/microAh) at end of bombardment and the contamination of 55Fe is only 0.008%.

Chromium Isotopes↗
PubMed1987

Production of gallium-66, a short-lived, positron emitting radionuclide.

The excitation functions for the production of 66Ga and some other radionuclides produced by the 4He-particle bombardment of a natural copper target have been measured up to 31 MeV incident energy. The radiochemical separation of 66Ga from the irradiated copper target as well as from the other radionuclides formed is described. The yield of 66Ga at 18 MeV incident energy is 708 microCi/microAh at end of bombardment and the contamination of 67Ga is 0.25%. The intended use of the 66Ga produced is to label monoclonal antibodies for PET scanning.

Gallium Radioisotopes↗
PubMed1986

Production of cobalt-55, a short-lived, positron emitting radiolabel for bleomycin.

The production and radiochemical separation of 55Co from deuteron irradiation of enriched 54Fe target is described. Methods used for the recovery and reuse of the target material (54Fe) are also described. The yield of 55Co at 12 MeV incident deuteron energy is 1.7 mCi per mu Ah at end of bombardment and the contamination with 57Co is 0.016%. The 55Co produced is chelated to bleomycin and used for tumour imaging with a positron emission tomographic camera based on multi-wire proportional chamber detectors.

Bleomycin↗