Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM. (1/45)

The 62Zn/62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. METHODS: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 microA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 microm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. RESULTS: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7+/-0.2 GBq (46.7+/-5.6 mCi), and yield was 72%+/-16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4%+/-2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8+/-0.2 GBq (20.5+/-5.3 mCi) with no adverse side effects. CONCLUSION: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.  (+info)

Simple new method for effective concentration of 188Re solutions from alumina-based 188W-188Re generator. (2/45)

(188)Re is a useful generator-produced radioisotope currently under evaluation for a variety of therapeutic applications, including bone pain palliation and intravascular radiation therapy. Because the (188)W parent is available only in a relatively low specific activity (<0.15-0.19 GBq/mg) from reactor irradiation of enriched (186)W, relatively large volumes of 0.9% saline (>15 mL) are required for elution of the (188)Re daughter from traditional alumina-based (188)W-(188)Re generators. Because these large bolus volumes result in solutions with a relatively low specific volume activity of (188)Re (<1 GBq/mL for the 18.5-GBq generator), the availability of effective methods for eluent concentration is important. Our new approach is based on the use of 0.3 mol/L ammonium acetate as a representative salt of a weak acid instead of saline for generator elution. METHODS: After generator elution, the ammonium acetate generator eluent (15-20 mL) is passed through a tandem IC-H Plus cation (Dowex-H)-anion (QMA Light) column system. Exchange of ammonium cations with hydrogen ions on the cation column forms an acetic acid solution containing perrhenate anions from which the macroscopic levels of the acetate anion of the eluent have been effectively removed. Because perrhenic acid is fully dissociated at this pH, the QMA Light column specifically traps the (188)Re-perrhenate, which is subsequently eluted with a low volume (<1 mL) of saline. Concentration ratios greater than 20:1 are readily achieved with this method. RESULTS: A typical clinical-scale generator loaded with 19.2 GBq (188)W was used to validate the approach. Saline elution provided (188)Re in a 75%-80% yield. Although elution with 0.15 mol/L NH4OAc gave lower yields (55%-60%), use of 0.3 mol/L NH4OAc provided yields comparable with those of saline (70%-75%). (188)W parent breakthrough was not detected after passage of the bolus through the tandem concentration system. Bolus volumes of 15-20 mL, which initially contained as much as 11.1-14.8 GBq (188)Re, were readily concentrated to less than 1 mL saline using QMA Light cartridges. The generator was evaluated for more than 3 mo with no decrease in performance. CONCLUSION: This approach represents a simple, rapid, and effective method using inexpensive disposable components of concentrating solutions of (188)Re for preparation of therapeutic agents.  (+info)

Genotypes associated with virulence in environmental isolates of Vibrio cholerae. (3/45)

Vibrio cholerae is an autochthonous inhabitant of riverine and estuarine environments and also is a facultative pathogen for humans. Genotyping can be useful in assessing the risk of contracting cholera, intestinal, or extraintestinal infections via drinking water and/or seafood. In this study, environmental isolates of V. cholerae were examined for the presence of ctxA, hlyA, ompU, stn/sto, tcpA, tcpI, toxR, and zot genes, using multiplex PCR. Based on tcpA and hlyA gene comparisons, the strains could be grouped into Classical and El Tor biotypes. The toxR, hlyA, and ompU genes were present in 100, 98.6, and 87.0% of the V. cholerae isolates, respectively. The CTX genetic element and toxin-coregulated pilus El Tor (tcpA ET) gene were present in all toxigenic V. cholerae O1 and V. cholerae O139 strains examined in this study. Three of four nontoxigenic V. cholerae O1 strains contained tcpA ET. Interestingly, among the isolates of V. cholerae non-O1/non-O139, two had tcpA Classical, nine contained tcpA El Tor, three showed homology with both biotype genes, and four carried the ctxA gene. The stn/sto genes were present in 28.2% of the non-O1/non-O139 strains, in 10.5% of the toxigenic V. cholerae O1, and in 14.3% of the O139 serogroups. Except for stn/sto genes, all of the other genes studied occurred with high frequency in toxigenic V. cholerae O1 and O139 strains. Based on results of this study, surveillance of non-O1/non-O139 V. cholerae in the aquatic environment, combined with genotype monitoring using ctxA, stn/sto, and tcpA ET genes, could be valuable in human health risk assessment.  (+info)

Federal regulations and reimbursement for PET. (4/45)

OBJECTIVE: The regulatory and reimbursement environment for PET has changed significantly over the past several years. The Food and Drug Administration's (FDA) findings of the safety and efficacy of key PET drugs have been published, as well as guidelines for the applications to produce PET drugs. In addition, the national Medicare coverage policy for PET has been expanded, most recently with additional indications and coverage restrictions added as of July 2001. The payment rates under the new Hospital Outpatient Prospective Payment System (HOPPS) have been set for PET as well. This communication reviews these recent changes and discusses their impact on the development and operation of a PET center. After reading this article, the nuclear medicine technologist should be able to: (a) state the indications for the use of PET drugs that have been found to be safe and effective by the FDA; (b) detail the general procedures a PET drug production site would have to undertake to be in compliance with FDA regulations; (c) list specific studies that have been approved for payment by Medicare; and (d) describe billing codes used for PET scans. Clarification of regulatory and reimbursement issues is leading to rapid expansion of clinical PET. Keeping abreast of these changes will ensure the successful expansion of any nuclear medicine program to include PET services.  (+info)

An assessment of factors which influence the effectiveness of the modified in vivo technetium-99m-erythrocyte labeling technique in clinical use. (5/45)

This study assessed factors which may contribute to suboptimal image quality when the modified in vivo erythrocyte labeling technique is used with standard clinical 99mTc activities. For each assessment duplicate or triplicate blood specimens were withdrawn from > or = 10 patients, into syringes containing 700-900 MBq 99mTc as pertechnetate. After incubation the percent of 99mTc which was not bound to erythrocytes at blood re-injection time (%Unbound 99mTc), was measured and compared when one of four factors was varied. The most significant results, in descending order of measured effect were: [table: see text] Our data suggest that the requirements for optimal erythrocyte labeling with standard clinical 99mTc activities are: (A) Erythrocyte tinning time between 10 and 30 min; (B) blood volume > or = 3 ml; (C) blood incubation time > or = 20 min; and (D) Generator ingrowth time < or = 24 hr.  (+info)

Realizing the potential of the Actinium-225 radionuclide generator in targeted alpha particle therapy applications. (6/45)

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Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies. (7/45)

The use of 188Re from an alumina-based 188W/188Re generator has been investigated for antibody radiolabeling. It was found that, with simple labeling techniques, 188Re can be used immediately after elution. The direct radiolabeling of intact antibodies with 188Re is described. Lyophilized antibody preparations have been reconstituted with 188Re taken directly from the generator at specific activities of up to 15 mCi of 188Re per mg of antibody. Radiolabeling yields of 90 to 98% have been obtained, with the incorporation rate being dependent upon time and the relative concentrations of the reagents. It was determined that the conjugates were immunoreactive and stable when challenged by serum in vitro, with 188Re-immunoglobulin G showing adequate resistance to reoxidation with no transfer of 188Re to serum protein. 188Re-antibody conjugates were shown to clear from the blood faster than the corresponding 131I-labeled antibody, giving rise to good tumor/nontumor ratios at 24 to 72 h postinjection, while serum samples taken from the animals have shown that the circulating 188Re remained bound to immunoglobulin G. The combination of the technologies of the 188W/188Re generator, the direct labeling methodology, and the use of single-vial lyophilized antibody makes the use of 188Re-radiolabeled monoclonal antibodies a simple and convenient method of cancer radioimmunotherapy with a beta-emitting radionuclide.  (+info)

Breaking America's dependence on imported molybdenum. (8/45)

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