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PubMed1980

Manganese-52m, a new short-lived, generator-produced radionuclide: a potential tracer for positron tomography.

A new generator system has been developed using the Fe-52 leads to Mn-52m parent-daughter pair. Fe-52, half-life 8.3 hr, is isolated on an anion-exchange column, and Mn-52m is eluted in hydrochloric acid. Breakthrough is less than 0.01% and the yield is 75%. The 21.1-min half life of Mn-52m is ideal for use in sequential studies, but is long enough to permit radiochemical manipulations to control biodistribution. Animal studies indicate that Mn-52m is an ideal nuclide for myocardial imaging, combining rapid blood clearance and high concentration in the myocardium. An added advantage is that Mn-52m decays 98% by positron emission and is useful for positron computer tomography.

Animals↗
PubMed2002

Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy.

We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

Cesium Radioisotopes↗
PubMed1990

Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion.

Generator produced positron-emitting radionuclides could potentially expand the application of positron emission tomography (PET) to centers that do not have access to a local cyclotron. The zinc-62/copper-62 radionuclide generator system could serve as a source of positron-emitting copper-62 (62Cu) (t1/2 = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/copper-62 generators capable of high output (greater than 300 mCi) and used the no-carrier-added eluate in a rapid high yield synthesis of [62Cu] Cu(PTSM) that provides the radiopharmaceutical in a form suitable for intravenous injection (where Cu(PTSM) = pyruvaldehyde bis(N4-methylthiosemicarbazonato) copper(II]. We then demonstrated in pilot studies that [62Cu]Cu(PTSM) provides high quality brain and heart images with PET, accurately delineating cerebral and myocardial perfusion in both experimental animals and in humans (corroborating results of previous experimental studies utilizing longer-lived copper isotopes). The results of this work demonstrate that 62Cu can be conveniently obtained from high-level generators and, when used to label Cu(PTSM), provides a generator-produced radiopharmaceutical capable of providing estimates of cerebral and myocardial perfusion independent of cyclotron-produced radionuclides.

Animals↗
PubMed1983

Gold-195m, an ultra-short-lived generator-produced radionuclide: clinical application in sequential first pass ventriculography.

Gold 195m (Au-195m) has a half-life of 30.5 sec and can be produced at the bedside from the parent mercury-195m (T 1/2 = 41.6 hr). The generator produced sterile pyrogen-free Au-195m with mercury breakthrough of 0.75 +/- 0.09 (s.e.m.) muCi per mCi of Au-195m. Approximately 20 to 25 mCi of Au-195m was produced per elution from a generator containing 155 mCi of Hg-195m. We compared first-pass resting Tc-99m angiograms with Au-195m angiograms in 28 patients. The correlation coefficient between the two studies was 0.92 over an ejection-fraction range from 0.22 to 0.83. In addition, we tested the reproducibility of Au-195m first-pass angiograms by performing two studies 3 min apart. In 25 patients with ejection fractions ranging from 0.20 to 0.78, the correlation coefficient between such pairs was 0.93. The nuclide is reliably and reproducibly produced, and its short half-life allows the performance of background-free sequential first-transit studies with unusually low radiation exposure to the patient.

Gold Radioisotopes↗
PubMed1977

An improved 191Os-191mIr generator for radionuclide angiocardiography.

191mIr is a useful tracer for radionuclide angiocardiography and may be of particular value in the evaluation of heart disease in children. It has a short half-life, a suitable photon energy, and may be obtained as a generator product by decay of its long-lived parent 191Os. A 191Os-191mIr generator capable of providing at least 18 mCi of 191mIr in 1.5 ml of eluant is described. 191mIr is separated from 191Os by absorbing 191OsCl6(-2) on an ion exchange resin and eluting with a solution of 8.7% NaCl at a pH of 2.2. The generator employs an additional resin column which is replaced to minimize 191Os breakthrough.

Animals↗
PubMed1991

Therapeutic radionuclides: production and decay property considerations.

The development of effective therapeutic radiopharmaceuticals requires careful consideration in the selection of the radionuclide. The in vivo targeting and clearance properties of the carrier molecule must be balanced with the decay properties of the attached radionuclide. Radionuclides for therapeutic applications fall into three general categories: beta-particle emitters, alpha-particle emitters, and Auger and Coster-Kronig-electron emitters following electron capture. Alpha particles and Auger electrons deposit their energy over short distances with a high LET that limits the ability of cells to repair damage to DNA. Despite their high levels of cytotoxicity, the relatively short range of alpha particles requires binding of the carrier molecule to most cancer cells within a tumor in order to be effective. Because of the extremely short range of Auger electrons, the radionuclide must be carried directly into the nucleus to elicit high radiotoxicity, making it necessary to deliver the radionuclide to every cell within a tumor cell population. These characteristics impose rigid restrictions on the nature of the carrier molecules for these types of particle emitters but successful targeting of these types of radionuclides could result in high therapeutic ratios. Most beta-emitting radionuclides are produced in nuclear rectors via neutron capture reactions; however, a few are produced in charged-particle accelerators. For radionuclides produced by direct neutron activation, the quantities and specific activities that can be produced are determined in large part by the cross-section of the target isotope and the flux of the reactor. Many applications (e.g., therapeutic bone agents, radiolabeled microspheres, radiocolloids) do not require high-specific activities and can therefore utilize the wide range of radionuclides that can be produced in sufficient quantity by direct neutron activation. Other applications (e.g., MAb labeling) require high-specific activity radionuclides in order to deliver a sufficient number of radionuclide atoms to the target site without saturating the target or compromising the integrity of the carrier molecule. Most radionuclides, produced at NCA levels in reactors, are produced via indirect reactions. High-specific activity beta emitters can also be obtained from radionuclide generator systems where the longer-lived parent radionuclide may be obtained from direct neutron activation, as a fission product, or from charged-particle accelerators. It is essential that the half-life of a radionuclide used in RNT be compatible with the rates of localization in target tissues and clearance of the carrier molecule from normal tissues. This consideration is especially important for the various MAbs and their fragments that are currently under investigation as carrier molecules to RIT.(ABSTRACT TRUNCATED AT 400 WORDS)

Half-Life↗
PubMed1983

A 195Hgm-195Aum generator for use in first-pass nuclear angiocardiography.

The development of a mercury-195m/gold-195m radionuclide generator system is described, together with the results of preliminary experiments in animals and in man. The daughter radionuclide has a half-life of 30.5 s with a principal gamma emission at 262 keV, ideal for use with the multicrystal camera but suitable also in conjunction with the Anger design. The half-life of the parent radionuclide is 40 h. The eluant in current use is 2.5 mM sodium cyanide, the column being stored under 2% sodium nitrate solution when not in use to prevent radiation damage. Generators capable of delivering 550 MBq of 195Aum in a 0.4 ml bolus have been used for first-pass nuclear angiocardiography, the half-life being long enough to permit administration via peripheral intravenous injection. The radiation dose associated with this radionuclide is much lower than that from conventional 99Tcm-labelled radiopharmaceuticals, permitting multiple sequential studies, even on children.

Animals↗
PubMed1987

Generator-produced yttrium-90 for radioimmunotherapy.

Yttrium-90 is often considered to possess many favorable properties for radioimmunotherapy applications. Among these is its availability as a radionuclide generator product by decay of its parent, 90Sr. Nevertheless, most present and planned clinical trials with 90Y-labeled antibodies employ radioactivity obtained not from an in-house generator, but from commercial sources. To prepare for clinical trials at this institution with 90Y labeled to diethylenetriaminepentaacetic acid- (DTPA) coupled antibodies, we have adapted previously published procedures and have developed others to prepare antibodies labeled with generator produced 90Y for human use. Up to 25 mCi of 90Sr have been loaded without evidence of radiolytic degradation to the Dowex 50 cation exchange resin which serves as the solid support for the generator. Using 0.003M ethylenetriaminetetraacetic acid (EDTA) as eluant, elution efficiency averages 98% and 90Sr breakthrough averages 0.002%. The EDTA is destroyed remotely and the activity is dissolved in 0.5M acetate, pH 6. In this form, 90Y may be used to label DTPA-coupled proteins at specific activities of 1-3 mCi/mg (an order of magnitude improvement in specific activity results from the purification of 90Y by cation exchange prior to labeling). When properly labeled, size exclusion HPLC shows 90% or greater radiochemical purity and recovery without postlabeling purification. We conclude that these techniques provide a 90Y-labeled protein preparation which is safe for administration to patients.

Animals↗
PubMed1992

Cyclotrons and positron emission tomography radiopharmaceuticals for clinical imaging.

Positron emission tomography (PET) requires positron-emitting radionuclides that emit 511-keV photons detectable by PET imagers. Positron-emitting radionuclides are commonly produced in charged particle accelerators, eg, linear accelerators or cyclotrons. The most widely available radiopharmaceuticals for PET imaging are carbon-11-, nitrogen-13-, and oxygen-15-labeled compounds, many of which, either in their normal state or incorporated in other compounds, serve as physiological tracers. Other useful PET radiopharmaceuticals include fluorine-18-, bromine-75-, gallium-68 (68Ga)-, rubidium-82 (82Rb)-, and copper-62 (62Cu)-labeled compounds. Many positron emitters have short half-lives and thus require on-site cyclotrons for application, and others (68Ga, 82Rb, and 62Cu) are available from radionuclides generators using relatively long-lived parent radionuclides. This review is divided into two sections: cyclotrons and PET radiopharmaceuticals for clinical imaging. In the cyclotron section, the principle of operation of the cyclotron, types of cyclotrons, medical cyclotrons, and production of radionuclides are discussed. In the section on PET radiopharmaceuticals, the synthesis and clinical use of PET radiopharmaceuticals are described.

Brain↗
PubMed1979

Potential column chromatography generators for ionic Ga-68. I. Inorganic substrates.

Chemical separations for Ga-68 from Ge-68 using adsorption chromatography on inorganic materials are described. The adsorbents used were TiO2, ZrO2, and SiO2. Distribution coefficients for Ge and Ga on these absorbents were determined as a function of reagent concentration and duration of equilibration. The distribution coefficient (w/w) for Ge on SiO2 reached 250 in 6 N HNO3, whereas Ga was no significantly adsorbed. Therefore, Ga-68 can be collected with a mall volume of 6 N HNO3 eluent. By contrast, large volumes of 1 N HNO3 were necessary to collect Ga-68 from ZrO2, since the KD of Ga under these circumstances was about 50. The Ga-68 eluted from TiO2 was chemically contaminated with titanates and would require additional chemical manipulation in order to make it injectable. All the adsorbents could lead to chromatographic systems that would allow acceptable chemical separations. However, the specific requirements for a radionuclide generator, usable in a hospital environment, make the SiO2-based system the most attractive.

Chromatography↗
PubMed1992

Cross sections of natSb(p,x) reactions for 30-46 MeV protons.

In order to optimize the production of 118Te in thick targets for use in a 118Te/118Sb radionuclide generator, the excitation function for the 121Sb(p,4n)118Te reaction has been measured for 30-46 MeV protons. The excitation functions for the competing reactions natSb(p,xn)119mTe, natSb(p,xn)119Te, natSb(p,xn)121mTe, natSb(p,pxn)120mSb and 123Sb(p,pn)122Sb have also been determined using stacked foil techniques. The 121Sb(p,4n)118Te reaction cross section maximum was found to be 480 mbarn at 44 MeV. In order to minimize the 119m + 119Te interference a minimum proton beam energy of 40 MeV is required. The cross section results are compared with published data and with calculated excitation functions.

Antimony↗