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Sample records for 99mtc-labelled radiopharmaceuticals version

  1. 99MTC-labelled autologous erythrocytes for the study of hepatic haemangiomas - Retrospective analysis

    Full text: Introduction: Haemangioma represents 5-7% of all benign tumours. Most hepatic lesions are easily diagnosed by ultrasound or CT scan, but sometimes differential diagnosis between haemangioma and other lesions is an important problem. Objectives: To evaluate the contribution of 99mTc-labelled autologous erythrocytes imaging for the diagnosis of hepatic haemangiomas. Population and Methods: We have retrospectively analysed, 61 patients (16(26%) males and 45(74%) females, with age> = 53 years) who have been submitted to hepatic study using 99mTc-labelled autologous erythrocytes (99mTc-LAE), between February 1999 and November 2002, for suspicious hepatic haemangioma. The hepatic lesions (diameter>=4,01±3,7cm) were documented by ultrasound and/or CT and/or MRI, none reaching a conclusive diagnosis: 39/61(64%) patients had single lesions, 8/61(13%) had two lesions, 5/61(8%) had three lesions and 9/61(15%) patients had more than 3 lesions. The erythrocytes in vivo labelling was performed with stannous chloride ev administration followed (by 20 minutes) by an 99mTc-Pertechnetate (740 MBq-20 mCi) ev administration. The hepatic images were made 2-3 hours after the administration of the radiopharmaceutical: 3 planar images (anterior, posterior and right lateral projections) and SPET. Results: 99mTc-LAE results were: 29 haemangiomas identified in 28/61(46%) patients, one of them also showing a lesion without elective erythrocytes accumulation; 6/61(10%) patients with lesions without elective erythrocytes accumulation; 27/61(44%) patients without any modification in the erythrocytes distribution parenchymal pattern. Lesion's dimensions (estimated by ultrasound, CT scan or MRI) were: haemangiomas identified by 99mTc-LAE - =5,27±3,3cm, 'cold' lesions in 99mTc-LAE - =2,58±1,47cm and non visualized lesions in 99mTc-LAE - =2,06±1,33cm. The 29 patients with haemangiomas, diagnosed in 99mTc-LAE, had already performed 25 ultrasounds, 20 CT scan, 5 MRI and 1 hepatic biopsy

  2. Radiopharmaceuticals

    The catalogue offers a wide-spread product range which meets the requirements of the international trend of in vivo application of radiopharmaceuticals. It includes: (1) conditions of sale and delivery, (2) delivery schedule for radiopharmaceuticals, (3) technical information, (4) product specifications, and (5) the complete delivery programme

  3. Radiopharmaceuticals

    Today there are an estimated ten million nuclear imaging procedures, performed each year, in just the United States, and the number is still growing. More than 30,000 therapy procedures are performed in the USA each year using radiopharmaceuticals. Moreover, while the numbers continue to grow, so also do the variety of the procedures being employed. A weakness of nuclear medicine is related also to one of its strengths. Unlike other types of imaging where only an instrument and the patient are required (e.g., with ultrasonics); nuclear medicine requires a radiopharmaceutical. At the same time, the variety of radiopharmaceuticals offers the ability to trace one or more particular functions of the human body. This provides nuclear medicine with great variety in detecting specific pathologies. Various nuclear medicine studies are possible because of the localization of radiopharmaceuticals in different organs

  4. Hospitable radiopharmaceuticals

    Two types of hospitalary radiopharmaceutical was given in Nuclear Medicine: the centralized and hospitalary radiopharmaceuticals. The good practice in the use, instrumentation and quality control of radiopharmaceuticals are used in nuclear medicine for diagnostic and therapy diseases

  5. Lung radiopharmaceuticals

    Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

  6. 6. Radiopharmaceuticals

    Radionuclides commonly used in medicine are surveyed and their nuclear characteristics are presented. The methods are given of their preparation, most frequent use and detection. The list is given of radiopharmaceuticals included in the Czechoslovak Pharmacopoeia CsL3, ie., sodium chromate(51Cr), sodium iodide(131I), hippuran(131I), sodium phosphate(32P), colloidal gold(198Au), rose bengal sodium salt(131I), and sodium pertechnetate(sup(99m)Tc) injections. Characteristics, chemical preparation, identification tests, packaging, storage, application and dosage are shown for each preparation. Also listed are important unofficial radiopharmaceuticals, their main characteristics and data on their preparation and application. (B.S.)

  7. Radiopharmaceutical assays

    Under the laws in force, radiopharmaceuticals for human use must be among other features, non-pyrogenous and non-toxic. For this reason pyrogenity and toxicity assays are carried out. Pharmacokinetic studies may also be necessary in some cases. Products currently made at the Radiopharmaceutical Center, new products designed for certification and raw materials used to manufacture the above, were tested. A total 342 pyrogenity and toxicity tests, and four pharmacokinetic studies were conducted in 1996. To determine pyrogenity, the temperature animals were measured following intravenous administration of radiopharmaceuticals concerned: sodium pertechnetate, colloidal gold and sodium orthoradiohippurate from current production; pharmaceutic components of several new products, i.e. technetium generator, fibrinogen and microspheres. A total 327 products were tested, 96 percent of which met the requirements. To determine toxicity, the probit method was used, consisting of the administration of radiopharmaceutical doses for seven straight days, and checking for lethal effects. An overall 15 tests were carried out and 80 percent of products tested were found certifiable. Pharmacokinetic tests consisted of tropism on target organs and biodistribution in several organs using the tomographic method. (author)

  8. Medicinal Radiopharmaceutical Chemistry of Metal Radiopharmaceuticals

    Saw, Maung Maung

    2012-06-01

    Metal complexes have been used as medicinal compounds. Metals have advantageous features over organic compounds. Significant applications of metal complexes are in the field of nuclear medicine. Radiopharmaceuticals are drugs containing radioisotopes used for diagnostic and therapeutic purposes. The generalized targeting strategy for molecular imaging probe consists of three essential parts: (i) reporter unit or payload, (ii) carrier, and (iii) targeting system. Medicinal radiopharmaceutical chemistry pays special consideration to radioisotopes, as a reporter unit for diagnostic application or as a payload for therapeutic application. Targeting is achieved by a few approaches but the most common is the bifunctional chelator approach. While designing a radiopharmaceutical, a range of issues needs to be considered including properties of metal radioisotopes, bifunctional chelators, linkers, and targeting molecules. Designing radiopharmaceuticals requires consideration of two key words: "compounds of biological interest" and "fit for intended use." The ultimate goal is the development of new diagnostic methods and treatment. Diagnostic metal radiopharmaceuticals are used for SPECT and PET applications. Technetium chemistry constitutes a major portion of SPECT and gallium chemistry constitutes a major portion of PET. Therapeutic radiopharmaceuticals can be constructed by using alpha-, beta minus-, or Auger electron-emitting radiometals. Special uses of medicinal radiopharmaceuticals include internal radiation therapy, brachytherapy, immunoPET, radioimmunotherapy, and peptide receptor radionuclide imaging and therapy.

  9. 99MTc labeled antimicrobial peptide ubiquicidin (29-41) accumulates less in E-coli infection as compared with staph. aureus infection

    99mTc labeled antimicrobial peptide ubiquicidin, UBI (29-41) in freeze-dried kit was evaluated as bacterial infection seeking agent in Staph. aureus and E-coli induced infections. Methods: 33 rabbits were categorized in three groups. Biodistribution of 99mTc UBI (29-41) was studied in three animals (group I). The uptake of peptide was determined by counting radioactivity in anatomically fitted regions drawn over the liver, kidneys, urinary bladder and whole body and expressed as percent uptake per organ. Experimental thigh muscle infection was induced by injecting 2 x 108 CFU of live Staph. aureus or E- coli bacteria into fight thigh muscle in 20 rabbits (group II). Turpentine oil and formalin killed Staph. aureus were utilized for inducing sterile thigh muscle inflammation in 10 rabbits (group III). On scintigrams, anatomically adjusted regions of interest (ROIs) were drawn over infected/inflamed (target) and non-infected/non-inflamed (non-target) thigh and accumulation of 99mTc-UBI (29-41) at sites of infection/inflammation was expressed as the target to non-target (T/NT) ratio. Results: Biodistribution study of 99mTc-UBI (29-41) revealed rapid removal of tracer from the circulation via the kidneys (10.6 ± 2.1% at 5 minutes and 5.9 ± 0.8% at 60 minutes) with accumulation of major part in urinary bladder within first hour after injection (66.6 ± 7.2%). Significantly higher (p < 0.05) accumulation of 99mTc-UBI (29-41) was seen at sites of Staph. aureus infected subjects (T/NT ratio 2.2 ± 0.5) as compared to E-coli (T/NT ratio 1.7 ± 0.4). Maximum tracer accumulation was observed at 60 minutes post-injection followed by gradual decline. No significant accumulation was noticed in thighs of rabbits injected with either turpentine oil or killed Staph. aureus with markedly lower T/NT ratios (p < 0.05) compared with Staph. aureus and E-coli infected thighs. Conclusion: 99mTc UBI (29-41) freeze-dried kit can be used for differentiating infections with Staph. aureus and E-coli with significantly higher scintigraphic intensity (P< 0.05) as compared to sterile inflammatory sites. Optimum time for infection imaging is 60 minutes post injection. Relatively low (T/NT) ratios were observed in E-coli infections as compared with Staph. aureus group which may be due to low virulence of the former, however there can be other possible reasons including low affinity of this peptide for E-coli microbial membranes. (authors)

  10. Radiopharmaceuticals for nuclear cardiology

    One of the diagnostic technique periodically used in Nuclear Medicine is the angiographic studi e, employee for detect cardiovascular diseases. The radiopharmaceutical more used in the angiographic ones is 99mTc. Between thetopics described in the present work it find: myocardial infarction, radiopharmaceuticals classification for cardiac studies, labelled proceedings, cardiovascular diseases

  11. FDA approved radiopharmaceuticals

    FDA is the abbreviation of American Food and Drug Administration. It s main job is assuring the safety and reliability of the food, cosmetics, medicines, medical devices and radiation emitting products such as microwave oven, the food and medicine for animals. Radiopharmaceuticals are also under its management. The basic information of FDA and FDA approved radiopharmaceuticals are introduced

  12. Radiopharmaceuticals for neurotransmitter imaging

    Oh, Seung Jun [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin transporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmaceuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [{sup 123}I] {beta} -CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [{sup 123}I]PE2I, [18F]FE-CNT, [{sup 123}I]FP-CIT and [{sup 18}F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [{sup 11}C]McN 5652 was developed for serotonin transporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [{sup 11}C]AFM and [{sup 11}C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

  13. Preparation of radiopharmaceutical formulations

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially 153samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs

  14. Radiopharmaceutical drug review process

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  15. Radiopharmaceuticals for cerebral studies

    For obtain good brain scintillation images in nuclear medicine must be used several radiopharmaceuticals. Cerebral studies give a tumors visual image as well as brain anomalities detection and are helpful in the diagnostic diseases . Are described in this work: a cerebrum radiopharmaceuticals classification,labelled compounds proceeding and Tc 99m good properties in for your fast caption, post administration and blood purification for renal way

  16. Undesirable events with radiopharmaceuticals

    Radiopharmaceuticals are used in nuclear medicine for diagnostic and therapeutic purposes. Many adverse reactions and false positive reactions related to radiopharmaceuticals take place every day in hospitals, but most of them are not reported. It is therefore important to understand the definition of each undesirable reaction. Adverse reactions are defined as any noxious or unintended reactions to a drug, which is administered in standard doses through the proper route for the purpose of prophylaxis, diagnosis, or treatment. False positive reactions can be defined as any imaging appearance caused by undue physiological or pathological accumulation of radiopharmaceuticals. Information concerning these undesirable reactions is limited for radiopharmaceuticals. The present study intends to be a source of information that could be accessed by all nuclear medicine staff. A review of the literature from 1957 to January 2009 was carried out using the criteria of a systematic review, established by the Cochrane Collaboration, an international non-profit organization, that provides up-to-date information about the health care. The present study has revealed that radiopharmaceuticals cause adverse reactions. Six cases of adverse reactions with radiopharmaceuticals were found: 2 cases with 18F-fluorodeoxyglucose (FDG) and 4 cases with technetium 99m (99mTc). Among the 4 cases of adverse reactions with 99mTc, one subject who received 99mTc-labeled sestamibi developed anaphylactic reactions. Moreover, a total of 8 cases with false positive reactions were found with FDG. In conclusion, a worldwide effort should be made to report as many cases as possible of adverse events and false positive reactions with radiopharmaceuticals. (author)

  17. Eleventh international symposium on radiopharmaceutical chemistry

    This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry

  18. Eleventh international symposium on radiopharmaceutical chemistry

    NONE

    1995-12-31

    This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry.

  19. Therapeutic applications of radiopharmaceuticals

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  20. Recent advances in radiopharmaceuticals

    Full text: Radiopharmaceuticals in Nuclear Medicine may be divided into diagnostic and therapeutic agents. The diagnostic area is perceived to be mature, while the therapeutic side of nuclear medicine is still evolving. There are over 100 diagnostic radiopharmaceutical products available, the greatest number applied in cardiology followed by oncology and neurology. The greatest success in therapeutic nuclear medicine has been achieved in thyroid cancer, hyperthyroidism and bone pain palliation. Those in the field believe the future of nuclear medicine resides in the growth potential of the emerging therapeutic market, hence much of the recent research has been focussed in the development of therapeutic agents for targeting cancers. Radiopharmaceuticals under development or in clinical trials involve the use of radionuclides such as Y-90, Pd-103, Ir-192, Re-188, I-131, Sm-153, Sn-114, Sr-90, Cu-64 and In-111. Advances in cyclotron and camera technology as well as automation has enhanced and widened the potential use of positron emitting radiopharmaceuticals such as F-18 Fluorodeoxyglucose (FDG). However the relationship between FDG uptake and glucose consumption in normal and diseased tissue is still to be defined. Many challenges remain for the nuclear medicine community to apply new knowledge of human biochemistry in the development of new radiopharmaceuticals. A better understanding of effects of radiation and its role in the design of therapeutic agents is undoubtedly pivotal for advancing therapeutic Nuclear Medicine into the future

  1. Cyclotron produced radiopharmaceuticals

    Kopička, K.; Fišer, M.; Hradilek, P.; Hanč, P.; Lebeda, O.

    2003-01-01

    Some of the cyclotron-produced radionuclides may serve as important materials for the production of radiopharmaceuticals. This lecture deals with basic information relating to various aspects of these compounds. In comparison with radionuclides/compounds used for non-medical purposes, radiopharmaceuticals are subject to a broader scale of regulations, both from the safety and efficacy point of view; besides that, there are both radioactive and medical aspects that must be taken into account for any radiopharmaceutical. According to the regulations and in compliance with general rules of work with radioactivity, radiopharmaceuticals should only be prepared/manufactured under special conditions, using special areas and special equipment and applying special procedures (e.g. sterilisation, disinfection, aseptic work). Also, there are special procedures for cleaning and maintenance. Sometimes the requirements for the product safety clash with those for the safety of the personnel; several examples of solutions pertaining to these cases are given in the lecture. Also, the specific role of cyclotron radiopharmaceuticals is discussed.

  2. Quality control of radiopharmaceuticals

    Quality assurance was introduced in the pharmaceutical field long before it was used in many other areas, and the term quality control has been used in a much broader sense than merely analytical quality control. The term Good Manufacturing Practice (GMP) has been used to describe the system used for producing safe and effective drugs of a uniform quality. GMP has also been used for the industrial production of radiopharmaceuticals. For the preparation and control of radiopharmaceuticals in hospitals a similar system has been named Good Radiopharmacy Practice (GRP). It contains the same elements as GMP but takes into account the special nature of this group of drugs. Data on the assessment of the quality of radiopharmaceuticals in relation to present standards are reviewed. The general conclusion is that the quality of radiopharmaceuticals appears comparable to that of other drugs. It seems possible to establish the production of radiopharmaceuticals, generators and preparation kits in such a way that analytical control of the final product at the hospital may be limited provided the final preparation work is carried out in accordance with GRP principles. The elements of GRP are reviewed. (author)

  3. Radiopharmaceuticals in oncology

    Radiopharmaceuticals are generally made of an artificial radionuclide chemically bound to a molecule showing an affinity for a particular type of cells. In oncology, the radionuclide emits either photons for scintigraphic imaging, either beta or alpha particles for metabolic radiotherapy. The development of new radiopharmaceuticals is mostly hampered by the modifications of conformation and hence, of biological behavior, of the original molecule induced by its radiolabelling. The use of positron emitters can be a solution to this difficulty, but their short half-life generates serious management limitations. Radiopharmaceutical used in oncology are targeted toward the cellular and tissular tumorous abnormalities. They belong to different categories: membrane agents, metabolic substrates (such as fluorodeoxyglucose), receptors ligands, antibodies and other agents under development such as hypoxia, apoptosis and genes markers. (authors)

  4. Radiopharmaceutical information and consultation services

    In this chapter, the authors, focus the discussion on: 1. The nature, scope, and depth of typical ''drug'' or ''radiopharmaceutical'' information questions that arise in nuclear medicine facilities and; 2. Possible approaches for handling and/or processing ''radiopharmaceutical'' information questions for nuclear medicine, along with exploration of the feasibility of establishing a radiopharmaceutical information center

  5. Audits of radiopharmaceutical formulations

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team

  6. Melanin-binding radiopharmaceuticals

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  7. Cyclotron produced radiopharmaceuticals

    Kopička, Karel; Fišer, Miroslav; Hradilek, Pavel; Hanč, Petr; Lebeda, Ondřej

    2003-01-01

    Roč. 53, č. 2 (2003), s. A763-A768. ISSN 0011-4626 R&D Projects: GA AV ČR KSK4055109 Keywords : cyclotron * radionuclides * radiopharmaceuticals Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 0.263, year: 2003

  8. Melanin-binding radiopharmaceuticals

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  9. Audits of radiopharmaceutical formulations.

    Castronovo, F P

    1992-03-01

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team. PMID:1598931

  10. Pain palliative Radiopharmaceuticals

    A pain relieving agents based on β emitters mainly and in some cases a complex preparation are being given for bone metastasis in relation with breast,prostate and lung carcinoma with good performance in clinical practice.Several radionuclides and radiopharmaceuticals are mentioned giving strength to those newly proposed, 153Sm and 186Re.Bibliography

  11. The development of cyclotron radiopharmaceuticals

    The purpose of this project is to develop the radiopharmaceuticals and automatic synthetic unit for labelled compounds, and to establish mass production system of radiopharmaceuticals. These will contribute to the early diagnosis of the disease hard to cure. The contents of this project are as follows, the development of the radiopharmaceutical for imaging of cancer, the development of automatic synthesizer for the synthesis of radio-pharmaceuticals, the development of hormone derivatives labelled with 12'3I, the development of the radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for imaging of myocardial metabolism

  12. The development of cyclotron radiopharmaceuticals

    Yang, Seung Dae; Chun, K. W.; Suh, Y. S.; Lee, J. D.; Ahn, S. H. and others

    1999-03-01

    The purpose of this project is to developthe radiopharmaceuticals and automatic synthetic unit for labelled compounds, and to establish mass production system of radiopharmaceuticals. These will contribute to the early diagnosis of the disease hard to cure. The contents of this project are as follows, the development of the radiopharmaceutical for imaging of cancer, the development of automatic synthesizer for the synthesis of radio-pharmaceuticals, the development of hormone derivatives labelled with {sup 12}'3I, the development of the radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for imaging of myocardial metabolism.

  13. Radioisotopes and radiopharmaceuticals catalogue

    The Chilean Nuclear Energy Commission (CCHEN) presents its radioisotopes and radiopharmaceuticals 2002 catalogue. In it we found physical characteristics of 9 different reactor produced radioisotopes ( Tc-99m, I-131, Sm-153, Ir-192, P-32, Na-24, K-42, Cu-64, Rb-86 ), 7 radiopharmaceuticals ( MDP, DTPA, DMSA, Disida, Phitate, S-Coloid, Red Blood Cells In-Vivo, Red Blood Cells In-Vitro) and 4 labelled compounds ( DMSA-Tc99m, DTPA-Tc99m, MIBG-I131, EDTMP-Sm153 ). In the near future the number of items will be increased with new reactor and cyclotron products. Our production system will be certified by ISO 9000 on March 2003. CCHEN is interested in being a national and an international supplier of these products (RS)

  14. Pharmacovigilance in radiopharmaceuticals

    Kumar, Rishi; Kalaiselvan, Vivekanandan; Kumar, Rakesh; Verma, Ravendra; Singh, Gyanendra Nath

    2016-01-01

    Indian Pharmacopoeia Commission is Committed for maintaining the standards of drugs including Radiopharmaceuticals (RPs) by publishing Indian Pharmacopoeia. These RPs are being used in India for diagnostic or therapeutic purpose. RPs though contain relatively small quantities of active ingredient and administered in small volumes could cause some adverse reactions to the patients. The objective of presenting this article is to introduce the system of adverse drug reaction reporting to the nuclear medicine fraternity who are dealing with RPs. PMID:27095855

  15. Radiopharmaceuticals for diagnosis

    During this grant period 1 January 1988--31 December 1990, we have successfully developed a number of new approaches to fluorine-18 labeled compounds, prepared several new radiotracers for both animal studies and eventual clinical trials, and explored the utility of a high-quality industrial robot in radiopharmaceutical applications. The progress during the last grant period is summarized briefly in the following sections. Publications arising from this research are listed below and can be found in Appendix I. 1 fig

  16. Good radiopharmaceuticals practices

    A careful security must be used in the nuclear medicine laboratory concerning to the proceedings, preparation and dispensation of radiopharmaceuticals. Each control laboratory must look after the radiation protection patients,workers and people in general. Between another routinary activities in the present work it find : equipment prearrangement,installations,handling and support of electronic instruments,proceedings,methodology, results and interpretation of analysis , as well as registry maintenance

  17. Radiopharmaceuticals for diagnosis

    Kuhl, D.E.

    1990-06-01

    During this grant period 1 January 1988--31 December 1990, we have successfully developed a number of new approaches to fluorine-18 labeled compounds, prepared several new radiotracers for both animal studies and eventual clinical trials, and explored the utility of a high-quality industrial robot in radiopharmaceutical applications. The progress during the last grant period is summarized briefly in the following sections. Publications arising from this research are listed below and can be found in Appendix I. 1 fig.

  18. Safety and efficacy of radiopharmaceuticals

    New radiopharmaceuticals are essential for further developments to take place in nuclear medicine. This book provides a systematic review of the phases involved in bringing a new radiopharmaceutical product from its conception into routine use. Scientists from the radiopharmaceutical industry, hospital pharmacies and the health authorities have contributed to this work. It includes all aspects from the design, chemical description, animal testing and radiation dosimetry to clinical trials and post marketing surveillance of adverse reactions and drug defects. The handling of radiopharmaceuticals in hospitals and the design of laboratory facilities ideal for the protection of personnel against radiation and protection of the product against environmental contamination are also covered. The quality control of radiopharmaceuticals prepared in the hospital is considered, taking into account the points of view held by industry, the hospitals themselves and the regulatory health agencies. This book provides a reference source for scientists involved in the development and testing of new radiopharmaceuticals. (orig.)

  19. Radiopharmaceuticals in cardiovascular diseases

    The high incidence of cardiovascular disorders and the attendant morbidity and mortality have encouraged the development of new radiopharmaceuticals for the diagnosis and localisation of coronary diseases. Myocardial perfusion imaging is an invaluable tool for the demonstration of transient ischemia and infarction in heart and identification of viable and non-viable myocardial tissue. Thallium chloride (Tl-201) is the agent currently in wide use but its drawbacks have been well recognised. Hence tremendous amount of research work has been carried out to develop a suitable Tc-99m radiopharmaceutical for this purpose which has resulted in the introduction of two Tc-99m labelled radiopharmaceuticals HEXAMIBI and BATO. These are being tried as myocardial imaging agents these days and the choice amongst these depends on concrete clinical situation. The experimental work involving the synthesis of ligand MIBI, formulation into freeze dried KIT form, quality control procedure, biodistribution studies and finally clinical evaluation of locally produced KIT in human volunteers has now been reported here. Our KIT has been produced for the first time in Pakistan and has been tried on forty five patients in Nuclear Medical Centre, AFIP (Rawalpindi). The results obtained are comparable to those of Ti-201 with a slightly higher liver background in case of MIBI but because of the easy availability MIBI has become agent of choice for myocardial perfusion studies. (author)

  20. Supply of radiopharmaceuticals in Japan

    Detailed statistics of the application of radiopharmaceuticals in nuclear medicine in Japan are summarized. They are the amount of supply in terms of monetary value and radioactivity, categorized usages of in vivo and in vitro, number of facilities using the radiopharmaceuticals for the time span of 5 years (1998-2002). Obvious tendency of decrease for in vitro use can be seen while the total amount of radiopharmaceuticals is almost unchanged. (author)

  1. Cyclotrons and positron emitting radiopharmaceuticals

    Wolf, A.P.; Fowler, J.S.

    1984-01-01

    The state of the art of Positron Emission Tomography (PET) technology as related to cyclotron use and radiopharmaceutical production is reviewed. The paper discusses available small cyclotrons, the positron emitters which can be produced and the yields possible, target design, and radiopharmaceutical development and application. 97 refs., 12 tabs. (ACR)

  2. Placental transfer of selected radiopharmaceuticals

    This paper reviews animal experiments carried out to determine the transfer of radiopharmaceuticals from mother to fetus. Animal data are compared to any human data available. The radiopharmaceuticals included in the discussion are Tc-99m pertechnetate, Tc-99m DTPA, Ga-67 citrate and Tl-201 chloride. (6 tab., 5 refs.)

  3. Cyclotrons and positron emitting radiopharmaceuticals

    The state of the art of Positron Emission Tomography (PET) technology as related to cyclotron use and radiopharmaceutical production is reviewed. The paper discusses available small cyclotrons, the positron emitters which can be produced and the yields possible, target design, and radiopharmaceutical development and application. 97 refs., 12 tabs

  4. Radiopharmaceuticals - current state and trends

    The current state as well as the tendencies of modern radiopharmaceutical development and application is reviewed. After an evaluation of the fundamental preconditions of decay characteristics and pharmaceutical properties the problems concerning sup(99m)Tc-radiopharmaceuticals, metabolizable compounds and the use of specific biological interactions are discussed. (author)

  5. Radiopharmaceuticals: therapeutic applications

    Radiopharmaceuticals are chemical compounds incorporating appropriate radionuclides, which are rendered suitable for human administration. It is the artificial production of radionuclide that laid the foundation of nuclear medicine. The basic principle in designing radiolabeled compounds for therapy is to achieve a high concentration of radioactivity in the target tissue which would be capable of delivering a desirable radiation dose with minimal exposure to the critical organ (usually bone marrow). With the availability of artificially produced radionuclides, therapeutic applications were initiated. Iodine-131 for the treatment of thyroid disorders has remained the most important one. Recent advances over the past 10 years are quite dramatic. There are three important areas where considerable research work is in progress. Intraarticular administration radiocolloids appear to be valuable for the management of synovitis in patients with rheumatoid arthritis. Palliative treatment of bone metastases and total-body bone marrow irradiation seem to be feasible with bone-seeking radiopharmaceuticals. Design and development of radiolabeled compounds for targeted delivery is important, such as (a) monoclonal antibodies for specific antigens, (b) peptides for specific receptors and (c) conjugated drugs for specific tumours. Radionuclide therapy is still in its infancy and present research activities reflect future potentials. (author). 76 refs., 4 figs., 2 tabs

  6. Molecularly targeted therapeutic radiopharmaceuticals

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  7. Development of new radiopharmaceuticals

    The possibilities to design and prepare better and more organ-specific radiopharmaceuticals for diagnostic nuclear medicine has increased dramatically in the recent past with a deeper understanding of the relationships between chemical structure and biological activity. Whereas most of the research is performed in well-funded laboratories of industrialized countries, there are several developing countries with adequate resources and expertise as to undertake fruitful research in the field of radiopharmacy. With the aim of promoting advanced research in radiopharmacy by developing new radiodiagnostics agents, in particular, hepatobiliary imaging agents labelled with 99mTc, and to facilitate exchange of information, the IAEA has established in 1983 the present Research Co-ordination Programme (CRP) with a duration of five years. The report includes detailed results obtained by all participants as well as novel preparation procedures for some of the newest and more promising radiopharmaceuticals developed under the auspices of the CRP. The extensive bibliographic reference listing is considered another important information of particular value for scientists in developing countries who do not always have access to updated scientific information sources. Refs, figs and tabs

  8. Melanin binding radiopharmaceuticals

    We have determined the biodistribution an uptake by the Greene melanoma in the Syrian golden hamster with 21 radiopharmaceuticals. Maximum % uptake and the time at which this occurred are listed. It is essential to know maximum tumor to background ration and the time after injection that this occurs to determine suitability for tumor scanning. The importance of species variation deserves mention. Detection of eye melanoma in humans was quite variable whereas in hamsters it was quite easy to obtain a positive scan with a single pinhole. We then looked at brain uptake in man and found it (the brain scan) to be significant. In addition, we found a high uptake by the lung, something not found in hamsters but not entirely unsuspected of a amine, such as 123I-4,3DMQ. Finally, our clinical experience has shown us some of the vagaries of melanoma-seeking radiopharmaceuticals. This reflects the complexity of melanin and melanin-binding and points out the necessity for a more detailed analysis of the mechanisms involved in melanin binding radionuclides

  9. Unconventional Nuclides for Radiopharmaceuticals

    Holland, Jason P.; Williamson, Matthew J.; Lewis, Jason S.

    2016-01-01

    Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission tomography (PET) and 99mTc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of “nonstandard” radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including β+, β−, γ-ray, and α-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy γ-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are discussed. PMID:20128994

  10. Instrumentation and radiopharmaceutical validation

    Although the promise of new positron emission tomography (PET) imaging agents is great, the process of bringing these agents to commercialization remains in its infancy. There are no PET products today that have gone through the full clinical and chemistry development process required to gain marketing approval by the US Food and Drug Administration (Fda). The purpose of this paper was to review validation from the perspective of the chemistry, manufacturing and controls (CMC) section of an Fda filing, as well as the validation requirements described in Fda good manufacturing practice (GMP) regulations, guidance documents and general chapters of the US Pharmacopoeia (Usp). The review includes discussion of validation from development to commercial production of PET radiopharmaceuticals with a special emphasis on equipment and instrumentation used in production and testing. The goal is to stimulate a dialog that leads to the standardization of industry practices and regulatory requirements for validation practices in PET.

  11. Organic radiopharmaceuticals: recent advances

    Organic radiopharmaceuticals are considered in light of accelerator and nuclide production requirements, special problems relating to the carrier-free state, including terminology, of the special technology required to prepare and manipulate these compounds and new trends in compound design and synthesis. The emphasis is on medical cyclotrons and the positron-emitting radionuclides, carbon-11, nitrogen-13, oxygen-15, and fluorine-18. New routes to synthetic precursors and organic compounds of high specific activity labeled with carbon-11, fluorine-18, and iodine-123 including monosaccharides, aromatic amines, neuroleptics, fatty acids, steroids, and other classes of compounds are discussed. Some compounds are considered in terms of the development and evaluation of structure-activity relationships and including some newer concepts such as metabolic trapping. 67 references

  12. Radiopharmaceuticals good practices handbook: ARCAL XV radiopharmaceuticals control and production

    A safety practice of the therapeutics diagnostic proceeding in nuclear medicine require a permanent provide high quality radiopharmaceuticals manufacture. This work treat to give a guide for all radio pharmacies laboratories that produce,control, fraction and or dispense radiopharmaceuticals products, with attention hospitable radiopharmacy laboratory. Three chapters with recommendations in manufacture good practice in Hospital radiopharmacy, industrial centralized, bibliography and three annexe's about clean area classification,standards work in laminar flux bell, and guarantee and cleaning areas

  13. Radiopharmaceuticals in breast milk

    As assessment has been made of the radiological hazards to an infant following the administration of a radiopharmaceutical to a breast feeding mother. Feeding should be discontinued after administration of most I-131 and I-125 compounds, Ga-67 citrate or Se-78 methionine, and for iodinated compounds where it was possible to resume feeding, a thyroid-blocking agent should be administered. For Tc-99m compounds, pertechnetate had the greatest excretion in milk and interruptions of 12hr and 4hr were considered appropriate for pertechnetate and MAA respectively. Other Tc-99m compounds, Cr-51 EDTA and In-111 leucocytes did not justify an interruption just on the grounds of their associated excretion in milk. The ingestion hazard could be minimized by reducing the administered activity, and in some cases, by the substitution of a radiopharmaceutical with lower breast milk excretion. For Tc-99m lung and brain scans, the absorbed dose due to radiation emitted by the mother (i.e. when cuddling) was less than the ingested dose, but for a Tc-99m bone scan the emitted dose was greater. In all three cases, the emitted dose did not exceed 0 x 5 mGy for the infant in close contact to the mother for one-third of the time. For In-111 leucocytes, the emitted dose was about 2mGy, and it was concluded that close contact should be restricted to feeding times during the first 3 days after injection. 36 references, 2 figures, 5 tables

  14. Biodistribution of radiopharmaceuticals - mathematic models

    Characteristic biodistributions of radiopharmaceuticals were investigated by means of mathematical pharmacokinetics. Beside linear concentration dependent transport processes the existence of chemical equilibria in corresponding compartments producing chemically different transport and permeating species were included. The derived relations have been demonstrated by mathematical organ models comprising the renal excretion, the distribution of an osteotropic radiopharmaceutical between the skelet and the tumour compartment as well as a kidney model. (author)

  15. Radiopharmaceuticals: State of the art

    The state of the art in radiopharmaceuticals is reflected by the major topics in the papers presented at the last three symposia on radiopharmaceuticals. For some time most papers have been devoted to positron emission topography compounds, followed closely by fluorine 18 and carbon 11 agents. Future progress in nuclear medicine will be determined both by the development of new, specific tracer agents and by improvements in the quality of the imaging devices. Steady progress is being made. (orig.)

  16. PET radiopharmaceuticals for neuroreceptor imaging

    2006-01-01

    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  17. Teaching and research in radiopharmaceuticals

    Radiopharmaceuticals comprise a critical element of diagnostic and therapeutic clinical nuclear medicine. As well they contribute to more basic pre-clinical and clinical diagnostic studies such as the evaluation of new drugs and new drug formulations. Their development and utilization is based on the complex interaction of a number of disciplines including medicine, pharmacy, biochemistry, pharmacology, chemistry, physics and engineering. This technically-complex multidisciplinary base has impeded the development of a uniform curriculum of training for basic scientists and professionals who work with radiopharmaceuticals. the range of technical knowledge required is very broad; it ranges from chemical synthesis and radiolabelling, through a maze of biochemistry, pharmacology and now molecular biology, to GMP manufacture, dispensing and clinical consultation concerning use and interpretation of data. Clearly, no single discipline can (nor should) be expected to undertake in-depth training of radiopharmaceutical scientists, but equally clearly, there is need for the development of curricula that will develop specific components of the essential knowledge base. The 'radiopharmaceutical' or 'product' orientation of both teaching and research can be used to provide a focus for academic and professional organizations to develop 'radiopharmacy' curricula that effectively train radiopharmaceutical practitioners for specific roles within the clinical, academic, government and industrial interests of radiopharmaceutical scientists. Currently, there is a plethora of segmented training programs, many of which are inadequately positioned to be of great value to the field or its practitioners. Efforts to re-focus radiopharmacy programs and to build professional recognition for them are bringing about harmonization of performance objectives, and leading to didactic and experiential curricula. The impact and evolution of regulatory processes will demand new and better

  18. Development of radiopharmaceuticals

    To overcome many problems caused by external radiation therapy, we have developed a new agent for internal radiation therapy, which is administered directly to the lesions and irradiate β-rays resulting in maximized therapeutic effect and minimized radiation damage to normal tissues or organs to nearby. In the same reasons, we have also developed a new radioactive patch for the treatment of skin cancer using β-emitting radionuclide. We prepared for 166Ho-chitosan complex (166Ho-CHICO) which is potential radiopharmaceuticals for the treatment of liver cancer, peritoneal cancer metastasized from stomach cancer, ovarian cancer, and rheumatoid arthritis in knee joints. We carried out various experiments such as evaluation of absorbed dosimetry, studies on absorption, distribution, metabolism, and excretion (ADME) and clinical trials with 166Ho-CHICO. For commercialization of 166Ho-CHICO, we evaluated its toxicity, efficacy and safety, and then prepared documents for submission to the Mininstry of Health and Welfare to get license as an investigational new drug. 166Ho-Patch for skin cancer treatment was prepared by neutron irradiation of pre-made non-radioactive 165Ho-Patch. We evaluated the efficacy and safety of 166Ho-Patch in the treatment of skin cancer using an animal model and in clinical cases. (author). 49 refs., 15 tabs., 36 figs

  19. Development of radiopharmaceuticals

    Park, Kyung Bae; Kim, J. R.; Shin, B. C.; Kim, Y. M.; Cho, U. K.; Han, K. H.; Chung, Y. J.; Shin, H. Y.; Hong, S. B.

    1997-09-01

    To overcome many problems caused by external radiation therapy, we have developed a new agent for internal radiation therapy, which is administered directly to the lesions and irradiate {beta}-rays resulting in maximized therapeutic effect and minimized radiation damage to normal tissues or organs to nearby. In the same reasons, we have also developed a new radioactive patch for the treatment of skin cancer using {beta}-emitting radionuclide. We prepared for {sup 166}Ho-chitosan complex ({sup 166}Ho-CHICO) which is potential radiopharmaceuticals for the treatment of liver cancer, peritoneal cancer metastasized from stomach cancer, ovarian cancer, and rheumatoid arthritis in knee joints. We carried out various experiments such as evaluation of absorbed dosimetry, studies on absorption, distribution, metabolism, and excretion (ADME) and clinical trials with {sup 166}Ho-CHICO. For commercialization of {sup 166}Ho-CHICO, we evaluated its toxicity, efficacy and safety, and then prepared documents for submission to the Mininstry of Health and Welfare to get license as an investigational new drug. {sup 166}Ho-Patch for skin cancer treatment was prepared by neutron irradiation of pre-made non-radioactive {sup 165}Ho-Patch. We evaluated the efficacy and safety of {sup 166}Ho-Patch in the treatment of skin cancer using an animal model and in clinical cases. (author). 49 refs., 15 tabs., 36 figs.

  20. New blood flow radiopharmaceutical

    Our program for research into the causes of mental disorders such as schizophrenia, manic depressive illness and senile dementia has led us to the development of a new radiopharmaceutical agent, IDNNA (4-iodo-2,5-dimethoxy-N,N-dimethylamphetamine). A series of some 15 different 131I labeled molecules with various substitutions on the amine were synthesized and tested, and the uptake of the 131I labeled conpounds in rats was measured. The dimethyl amine (IDNNA) had the best brain uptake and brain/blood ratio. When injected into a dog and scanned with a whole-body scanner, the uptake in the brain could be clearly seen and quantified. Plasma sampling at the same time showed that the maximum brain/blood ratio of 8.7 occurred at 8 min after injection, and the concentration in brain remained high for at least 15 min. Labeling is achieved by reacting 131ICl and the precursor, 2,5-dimethoxy-N,N-dimethyl amphetamine, in glacial acetic acid; the reaction is complete in less than one minute

  1. Radiopharmaceuticals targeting melanoma

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  2. Radiopharmaceuticals for hepatobiliary imaging

    Chervu, L.R.; Nunn, A.D.; Loberg, M.D.

    1982-01-01

    Tests for liver function have by and large centered around clinical laboratory diagnostic procedures for a number of years. Besides these, radiographic imaging procedures, including oral cholecystography and intravenous cholangiography, serve a very useful purpose, but several of them are invasive and involve a certain degree of risk from the administered contrast media as well as discomfort to the patient. The cholescintigraphic procedures, though noninvasive, have not played a significant role in the evaluation of hepatobiliary disorders prior to the introduction of the currently available /sup 99m/Tc-labeled IDAs. These new hepatobiliary agents offer many advantages over the previously utilized radiopharmaceuticals (/sup 131/I-rose bengal in particular) in terms of the high degree of specificity for localization in the gallbladder with rapid extraction rates by the polygonal cells of the liver and very low excretion via the GU tract. A detailed understanding of the structure distribution relationship of the various groups in the complex enable the design of agents with an improvement in hepatobiliary specificity and other desirable characteristics. In many clinical situations, even in patients with high bilirubin levels, the /sup 99m/Tc-labeled IDAs offer far superior clinical information over the alternative diagnostic imaging modalities. Further, the absorbed radiation dose imparted to the critical organs is far lower than with the older agents. Thus, the introduction of the cholescintigraphic procedures with the /sup 99m/Tc-labeled IDAs have ushered in a new phase in the diagnostic workup of patients with impaired hepatocellular function and other biliary disorders.

  3. Comparative evaluation of therapeutic radiopharmaceuticals

    Radionuclide therapy employing unsealed radiotherapeutic agents has emerged as an important tool for cancer management. The development of therapeutic radiopharmaceuticals based on different types of carrier molecule and a variety of radioisotopes is being actively pursued worldwide. There have been many significant advances in this field, and many of the technical problems involved in labelling biomolecules with a variety of radionuclides have been solved. However, the assessment of the relative effectiveness of different radiopharmaceuticals for cancer therapy is a difficult task owing to the large number of variables that must be considered, some related to the biological carrier and others to the radioisotope. Comparing the therapeutic efficacy in patients is not feasible in most cases for ethical and regulatory reasons. Hence, it is important to develop laboratory methods that can be used for reliable and efficient comparative evaluation of promising therapeutic radiopharmaceuticals. The IAEA has organized several coordinated research projects (CRPs) in the field of radiopharmaceuticals that have helped Member States to acquire technologies for the production of useful radiopharmaceuticals. In one such CRP on techniques for labelling biomolecules for targeted therapy, conducted from 1998 to 2001, the participants developed several protocols and standard operating procedures for labelling peptides and antibodies with therapeutic radioisotopes. During the course of the CRP, it was recognized that successful development of therapeutic radiopharmaceuticals will require in vitro biological assays as well as appropriate tumour models for carrying out biodistribution studies of the products in order to collect data for preclinical studies. Two meetings, held in 1999 and 2001, recommended the organization of a CRP for the development of laboratory methods for comparative evaluation of therapeutic radiopharmaceuticals. Fifteen countries - Brazil, Cuba, the Czech

  4. R and D of radiopharmaceuticals at SINR

    The current status and market trend of the radiopharmaceuticals are discussed in detail. The establishment of the Shanghai Joint R/D Center of Radiopharmaceuticals, under the Chinese Academy of Sciences and the State Administration of Pharmaceuticals of China, will greatly promote the research, development and industrialization of the cyclotron-based radiopharmaceuticals for the SPECT and PET applications

  5. Molecular modelling and radiopharmaceutical design

    Aim: Among several headings for radiopharmaceuticals (RPs) design, molecular modelling (MM) could be used for the prediction of ligands and metal-complexes structures. Using MM it is also possible to simulate molecular interactions between predicted structures and specific biomolecules. Bisphosphonates (BPs) are ligands that are able to coordinate radioactive metals, such as 153Sm, 166Ho, 186Re, etc., but they are all polymeric complexes difficult to characterize. It is reported that the bone uptake does not depend on the nature of metal center, but is primarily driven by the nature of the ligand, as in the case of HEDP-M (M=99mTc, 186Re, 113Sn). So, it would be interesting to estimate the relevant molecular properties of BPs by MM, simulate their interaction with hydroxyapatite (HAP) the main bone component, and then correlate the predicted molecular parameters with experimental data obtained from HAP binding and biodistribution studies of BPs carrying radioactive metals. Materials and Methods: The molecular structures and preferred conformations of BPs differing in the length of the aliphatic chain attached to their substituted amine groups (pami-dronate, olpadronate and ibandronate) were obtained using the second-generation CVFF 950 (version 1.01) force field of Hwang et al. Simulation of the interactions between the studied BPs and HAP were performed using a Cerius-2 system of programs running on a Silicon Graphics O2 workstation. BPs-153Sm complexes were synthesized and characterized by ITLC. Their binding to HAP and in vivo biodistribution studies were carried out as usual described in literature. Results: A direct correlation could be established between in vitro BPs affinity towards HAP and their corresponding energies from the Coulomb interactions involving the N and P atoms of the studied BPs bound to the HAP (0,0,1) surface and the nearest Ca atoms of HAP. The BPs-153Sm showing the highest binding to HAP and skeletal uptake are those which possess the

  6. Radiochemical stability of radiopharmaceutical preparations

    Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Oliveira, Ideli M. de; Felgueiras, Carlos F.; Herrerias, Rosana; Zapparoli Junior, Carlos L.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The 'in vitro' stability studies of the radiopharmaceutical preparations are an essential requirement for routine practice in nuclear medicine and are an important parameter for evaluating the quality, safety and efficacy required for the sanitary registration of pharmaceutical products. Several countries have published guidelines for the evaluation of pharmaceutical stability. In Brazil, the stability studies should be conducted according to the Guide for Conducting Stability Studies published in the Resolution-RE n. 1, of 29th July 2005. There are also for radiopharmaceutical products, two specific resolutions: RDC-63 regulates the Good Manufacturing Practices for Radiopharmaceuticals and RDC-64 provides the Registration of Radiopharmaceuticals, both published on the 18th December 2009. The radiopharmaceutical stability is defined as the time during which the radioisotope can be safely used for the intended purpose. The radiochemical stability can be affected by a variety of factors, including storage temperature, amount of radioactivity, radioactive concentration, presence or absence of antioxidants or other stabilizing agents. The radiochemical stability studies must be established under controlled conditions determined by the effective use of the product. The aim of this work was to evaluate the radiochemical stability of labeled molecules with {sup 131}I, {sup 123}I, {sup 153}Sm, {sup 18}F, {sup 51}Cr, {sup 177}Lu and {sup 111}In as well as {sup 67}Ga and {sup 201}Tl radiopharmaceuticals. Radiochemical purity was evaluated after production and in the validity period, with the maximum activity and in the recommended storage conditions. The analyses were carried out by thin-layer silica gel plate, paper chromatography and gel chromatography. The experimental results showed to be in accordance with the specified limits for all the analysed products. (author)

  7. Prenatal radiation doses from radiopharmaceuticals

    The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author)

  8. Radiopharmaceuticals for palliative therapy pain

    Dissemination to bone of various neoplasms is cause of pain with poor response by major analgesics.Indications. Radiopharmaceuticals,description of main characteristics of various β emitter radionuclides.Choose of patients for worm indication of pain palliative therapy with β emitter radiopharmaceuticals is adequate must be careful . Contraindications are recognized.Pre and post treatment controls as clinical examination and complete serology are described.It is essential to subscribe protocols,keep patient well informed,included the physician in charge of the patient as part of the team.Bibliography

  9. Preparation of radiopharmaceuticals labeled with metal radionuclides

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides

  10. Specific GMP guidelines for radiopharmaceutical products

    These guidelines are intended to complement those provided in ''Good manufacturing practices for pharmaceutical products'', as well as the GMP for sterile pharmaceutical products. The regulatory procedures necessary to control radiopharmaceutical products are in large part determined by the sources of products and methods of manufacture. Manufacturing procedures within the scope of these guidelines include: preparation of radiopharmaceuticals in hospital radiopharmacies, preparation of radiopharmaceuticals in centralized radiopharmacies, production of radiopharmaceuticals in nuclear centres, institutes or industrial manufacturers, preparation and production of radiopharmaceuticals in Positron Emission Tomography (PET) centres

  11. Preparation of radiopharmaceuticals labeled with metal radionuclides

    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  12. Lymphoscintigraphy: radiopharmaceutical selection and methods

    Kramer, E.L. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1990-01-01

    The range of radiopharmaceuticals available for lymphoscintigraphy including radiocolloids, radiolabeled macromolecules and monoclonal antibodies are briefly discussed. The techniques used for tumour staging in internal mammary lymphoscintigraphy, iliopelvic lymphoscintigraphy, peripheral lymphoscintigraphy, localization of 'at risk' lymph nodes and lymphedema are also reviewed. (UK).

  13. Radiopharmaceuticals preparation following hygienic rule

    The rules of radiation protection are essential in a service of nuclear medicine. A sensitization to hygiene in hospital in front of the fresh outbreak of nosocomial infections is useful in order to optimize the quality approach. In this context, the preparation of radiopharmaceuticals in the structure of nuclear medicine deserves a specific reflection. (N.C.)

  14. Current directions in radiopharmaceutical research

    Much of current radiopharmaceutical research is directed towards the development of receptor-binding tracers which are targeted towards biochemical processes. These may be extra or intracellular in nature and hold promise for an imaging approach to tissue characterisation in-vivo. Many of these products are based on proteins which range in size from large monoclonal antibodies to small neuropeptides and share a radiolabelling chemistry based on the use of bifunctional chelating agents. Although developed initially for use with indium-111, considerations of cost and isotope availability have continued to direct the efforts of many researchers towards the use of technetium-99m. While polypeptide-based radiopharmaceuticals may be useful for imaging peripheral cell-surface receptors, access to sites of interest within the cell, or in the brain, requires the development of small lipophilic molecules with retained ability to interact with intracellular targets. The design and synthesis of these compounds presents a particular challenge to the radiopharmaceutical chemist which is being met through either a pendant or integrated approach to the use of technetium coordination with particular emphasis on technetium (v) cores. Progress continues to be made in the application of targeted radionuclide therapy particularly in the development of radiopharmaceuticals for the treatment of malignant bone disease. methods for labelling antibodies with a great variety of cytotoxic radionuclides have now been refined and their use for radioimmunotherapy in the treatment of haematological malignancies shows great promise. The major medical areas for application of these new radiopharmaceuticals will be in oncology, neurology and inflammation but the increasingly difficult regulatory climate in which drug development and health-care now operate will make it essential for researchers to direct their products toward specific clinical problems as well as biological targets. (author)

  15. Radiopharmaceuticals for diagnosis. Final report

    1994-03-01

    In the period 1969-1986, this project was directed to the evolution of target-specific labeled chemicals useful for nuclear medical imaging, especially radioactive indicators suited to tracing adrenal functions and localizing tumors in the neuroendocrine system. Since 1986, this project research has focused on the chemistry of positron emission tomography (PET) ligands. This project has involved the evaluation of methods for radiochemical syntheses with fluorine-18, as well as the development and preliminary evaluation of new radiopharmaceuticals for positron emission tomography. In the radiochemistry area, the ability to predict fluorine-18 labeling yields for aromatic substitution reactions through the use of carbon-13 NMR analysis was studied. Radiochemical yields can be predicted for some structurally analogous aromatic compounds, but this correlation could not be generally applied to aromatic substrates for this reaction, particularly with changes in ring substituents or leaving groups. Importantly, certain aryl ring substituents, particularly methyl groups, appeared to have a negative effect on fluorination reactions. These observations are important in the future design of syntheses of complicated organic radiopharmaceuticals. In the radiopharmaceutical area, this project has supported the development of a new class of radiopharmaceuticals based on the monoamine vesicular uptake systems. The new radioligands, based on the tetrabenazine structure, offer a new approach to the quantification of monoaminergic neurons in the brain. Preliminary primate imaging studies support further development of these radioligands for PET studies in humans. If successful, such radiopharmaceuticals will find application in studies of the causes and treatment of neurodegenerative disorders such as Parkinson`s disease.

  16. Radiopharmaceutical: options to marketing authorization

    In France, since the law 92-1279 (December 1992) the tracer used in nuclear medicine are considered as medicines, and all the regulations applicable to general medicines have to be followed for radiopharmaceuticals. The best situation in order to use radiopharmaceutical in nuclear medicine center is to use a tracer with a marketing authorization. However due to the very high cost to obtain this authorization, many tracers validated by scientific community will never been sold by pharmaceutical companies. However in respect with legal rules, it is possible to prepare these tracers in the hospital radiopharmacy, under the responsibility of the radio-pharmacist. We discuss here these different possibilities (magistral preparation...) and the conditions for these preparations. (author)

  17. Radiopharmaceutical transport system in France

    Radiopharmaceuticals are transported in type A package, activities are low and distributed among more than 200 000 packages sent throughout France. Impact of ICRP recommendations and of French regulations on packaging, storage, handling and transport is underlined. Road, rail or air transport are determined by geographical consideration and importance of each means of transport concerning quantities or mileage are easily deduced. Risks for normal conditions are evaluated. Accidents or incidents are rare and statistic analysis non-significant. 7 refs

  18. Radiation dose estimates for radiopharmaceuticals

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms

  19. Development of radiopharmaceutical for radiosinovectomy

    Radiopharmaceuticals prepared with different radionuclides have been used in diagnostic and therapeutic procedures in Nuclear Medicine. The interest in radionuclidic therapy has been increased in last years, with the introduction of new radiopharmaceuticals applied in the destruction of specific cells or to prevent its undesired proliferation. Radiosinovectomy (RSV) is a therapeutic modality that uses radiopharmaceuticals administered in the intra-articular cavity and represents an alternative to the treatment of different arthropaties and, in particular, the arthropaties derived from rheumatoid arthritis and haemophilic. The objective of the present work was to study the labeling of compounds with 90Y and 177Lu in order to improve the production conditions and quality control procedures, study the stability of the labeled compounds and preliminary biodistribution studies of the radiopharmaceuticals with potential for RSV applications. The study of the production of 90Y citrate colloid (90Y-Cit) was based in a labeling procedure using 90Y Cl3 solution (37 - 54 MBq) that was previously dried, followed by the addition of yttrium nitrate and sodium citrate in p H 7 at 37 deg C for 30 minutes. The production of hydroxyapatite (HA) labeled with 90Y was based in a labeling procedure using mono hydrated citric acid, yttrium nitrate and 90Y Cl3 solution (37 - 370 MBq). The reaction mixture was incubated for 30 minutes at room temperature and the HA was introduced in aqueous medium and the reaction proceed for 30 minutes under strong stirring. 177Lu-HA was produced using 177Lu Cl3 solution (296 MBq), in presence of lutetium oxide in NaCl medium, p H 7, under continuous stirring for 30 minutes at room temperature. Several reaction parameters were studied for the three radiopharmaceuticals. Labeling yield was determined after particles were centrifuged and washed with NaCl 0,9%. Radiochemical purity was determined by ascending chromatography using different chromatographic

  20. Preparation and control of radiopharmaceuticals in hospitals

    This guidebook covers the work commonly organized as part of the work in the hospital. It does not cover the manufacture of radiopharmaceuticals on an industrial scale. The work is characterized by the small scale on which manufacture and preparation of radiopharmaceuticals take place

  1. Quality control in 99m technetium radiopharmaceuticals

    This work means about the quality control in Tc radiopharmaceuticals preparation at hospitalary levels. Several steps must be used in a Nuclear Medicine Laboratory, such as proceeding,radiopharmaceuticals kits preparation, and dispensation materials,glasses,stopper,physical aspects,identification,ph control,storage,and reactif kits

  2. Radiopharmaceuticals based on antibodies and peptides

    The past two decades have seen a great stride in the development of new diagnostic and therapeutic radiopharmaceuticals due to the discovery and availability of a number of specific carrier molecules and the application of synthetic organic chemistry to modify these carrier molecules to accommodate the radionuclide of interest. Radiopharmaceuticals based on antibodies and peptides are discussed

  3. Radiopharmaceuticals. 40 years is nothing

    The nuclear medicine is today a medical speciality recognized and practised in the whole world. The birth was in the middle of the 20th century in the use of molecules or drugs marked with a radionuclide (radiopharmaceutical), for the diagnostic studies in vivo or in vitro, to obtain a therapeutic effect. Early in the decade of 70, its development and evolution was accentuated thanks to electronics, the contribution of new instruments for detection of diagnosis by images (gamma camera) and to the emergence of new radionuclide (in particular, 99mTc). (author)

  4. Biochemical considerations in the design of radiopharmaceuticals

    The goal of radiopharmaceutical chemistry is to design and develop radiotracers targeted to an organ or function whose activity kinetics in tissue can be detected externally by a gamma or a positron device. Radiopharmaceuticals are divided into the general categories of specific and non-specific agents. The specific radiopharmaceuticals are the tracers that follow a biochemical pathway or are involved in a particular interaction, for example metabolic substrates, drugs or analogs, and antibodies. This paper will focus on trends in the design of specific agents. The best radionuclides for the development of specific tracers are the positron emitting nuclides: carbon-11, nitrogen-13, oxygen-15 and fluorine-18. First the design of radiopharmaceuticals are considered in general (labeling strategies, stereochemical effects, specific activity). Next, a brief summary of the use of several radiopharmaceuticals is presented on the basis of their biochemical rationale. (orig./G.J.P.)

  5. Clean room installations in a radiopharmaceutical facility

    The standards of radiopharmaceuticals on the facility, working environment and preparation control strategy are yet to be generated. In general, radiopharmaceuticals have short half-lives and emit gamma radiation. Due to its unique characteristics, its preparation has to be made in the fume hood and hot cell to avoid radiation exposure to workers. Considering radiation protection, the working environment has to be maintained under negative pressure so that dispersion of radiopharmaceuticals should be avoided. On the contrary, a positively pressurized working environment gives clean atmosphere and prevents contamination with harmful microorganisms during preparation. Hence, it is required to harmonize for mentioned contradictory conditions in preparation of radiopharmaceuticals for the safety of workers and its quality assurance as well. Therefore, it is reasonable that good manufacturing practice for radiopharmaceutical production facility should be constituted according to the standards for production of biological agents accompanied with a radiation shielding

  6. Production of radiopharmaceuticals by cyclotrons

    Companies specialized in the development and installation of accelerator-based systems dedicated to the medical applications brought on the market cyclotrons well fitted to the requests of the industrial community or universities and so covering every segment of the market. These machines are fully automatic, and need reduced maintenance; they are highly specialized for defined tasks. They can produce high beam intensity and realize dual beam irradiation. Also the prices are reducing considerably. The targets and the automatic system follow the same trend. Unfortunately, the flexibility of these devices for new area of research and development has been dramatically reduced. The growing number of PET cameras has increased the popularity of PET tracers used for nuclear imaging. Consequently, there is a growing demand for these radiopharmaceuticals compounds labeled with short-lived radioisotopes for clinical applications. From a research and development tool in the eighties, PET has now grown up to a clinical tool. Moreover, depending of the social welfare, reimbursement of some PET examinations is granted, which accelerates the trend for an extended use of PET tracers. Regulatory affairs try to establish and standardize the control on these radiopharmaceutical compounds produced in a growing number of local radio pharmacies owning a baby cyclotron. On the other hand, the attention of equipment suppliers was brought in the setting up of a total quality control follow up. These efforts were successively achieved by getting for instance the ISO 9001 certificate

  7. Radiopharmaceuticals production activities in Egypt

    Applications of radiopharmaceuticals and labelled compounds in the field of nuclear medicine in Egypt have increased so rapidly in the last few years. At present, a large number of hospitals are utilizing these radioisotopic techniques for both diagnosis and treatment. The following production activities are taking place in the Egyptian Radioisotope Production laboratories. By utilizing the research reactor a large number of radioisotopes which find wide applications in nuclear medicine were produced, such as iodine-131, phosphorus-32, sodium-24, potassium-42 and molybdenum-99 / technetium-99m generators. Gallium-67, indium-111 and iodine-123 will be produced locally after installation of the cyclotron at the end of 1998. A large number of Tc-99m based kits for diagnostic medical applications have been produced. Also, many radiopharmaceuticals labelled with iodine-131 were produced. The radioisotope production laboratory is able to supply many hospitals with the radioimmunoassay kits of the thyroid related hormones (T4, T3 and TSH). Research and development activities are taking place in the field of monoclonal antibodies and tumor markers with special consideration of AFP, CEA, PSA and βhCG. (author)

  8. Fourth international radiopharmaceutical dosimetry symposium

    The focus of the Fourth International Radiopharmaceutical Dosimetry Symposium was to explore the impact of current developments in nuclear medicine on absorbed dose calculations. This book contains the proceedings of the meeting including the edited discussion that followed the presentations. Topics that were addressed included the dosimetry associated with radiolabeled monoclonal antibodies and blood elements, ultrashort-lived radionuclides, and positron emitters. Some specific areas of discussion were variations in absorbed dose as a result of alterations in the kinetics, the influence of radioactive contaminants on dose, dose in children and in the fetus, available instrumentation and techniques for collecting the kinetic data needed for dose calculation, dosimetry requirements for the review and approval of new radiopharmaceuticals, and a comparison of the effect on the thyroid of internal versus external irradiation. New models for the urinary blader, skeleton including the active marrow, and the blood were presented. Several papers dealt with the validity of traditional ''average-organ'' dose estimates to express the dose from particulate radiation that has a short range in tissue. These problems are particularly important in the use of monoclonal antibodies and agents used to measure intracellular functions. These proceedings have been published to provide a resource volume for anyone interested in the calculation of absorbed radiation dose

  9. Radiopharmaceuticals drug interactions: a critical review

    Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here, we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions. (author)

  10. Uncertainty sources in radiopharmaceuticals clinical studies

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  11. Dosimetry for radiopharmaceuticals (invited paper)

    Developments in internal dosimetry for radiopharmaceuticals are summarised, with special reference to work carried out within the International Commission on Radiological Protection (ICRP). Differences and similarities with internal dosimetry for occupationally exposed workers and for members of the public are identified. What is unique for radiopharmaceuticals is their special biokinetics. The products are designed to get high uptake in certain organs and tissues. When a new compound is introduced there are few long-term retention data for humans available. Therefore efforts have continuously to be made to investigate the biokinetics and dosimetry of new products as well as older products, for which the dosimetry is uncertain, e.g. pure β-emitters. Serial, quantitative gamma camera images of patients will continue to be the base for biokinetic information together with analysis of urine samples. The observed time-activity curves are described using exponential functions with specified fractional activities and half-times. The physical calculations are based on the MIRD formalism. For more detailed dosimetry, CT, MR and ultrasound can be used to localise organs and to determine their volumes. Such measurements are also needed for the construction of realistic phantoms (mathematically describable phantoms, 'voxel' phantoms and anthropomorphic phantoms) which are the geometrical base for dose calculations. Variations in anatomy and biokinetics between individuals due to age, gender and disease have to be given greater consideration in the future. Information on the distribution of a radionuclide within organs and tissues is of importance for its therapeutic use as is the intracellular localisation of low energy electron emitters both in therapy and diagnosis. (author)

  12. Radioisotopes and radiopharmaceuticals in nuclear cardiology

    Nuclear medicine studies of the heart represent one of the fastest growing areas of research and clinical interest. Some years ago, nuclear medicine cardiac studies were limited to the evaluations of myocardial infraction. Developments in radiopharmaceuticals chemistry and instrumentation have made possible advances in cardiovascular nuclear medicine. Techniques and Radiopharmaceuticals no exist for the imaging of viable myocardium and the determination of myocardial tissue metabolism, as well as radionuclide angiography to obtain quantitative information of cardiac output, mean transit times, cardiac volumes, and ejection fractions. This paper will firstly describe that anatomy and physiology of the heart as to relate to the radiopharmaceuticals which will be discussed, and will secondly explore various radiopharmaceuticals which have been used for various purposes in cardiac imaging, than will explore radioisotopes which have been proposed for myocardial treatment

  13. Report of the Task Force on radiopharmaceuticals

    The procedures for evaluation of IND and NDA applications were reviewed by FDA and the state members of the Task Force believe that there is significant progress being made toward expeditious handling of these items. Progress toward publication of the final rule on radiopharmaceuticals has reduced the need for state regulatory activity in investigational aspects of radiopharmaceutical research to the point that the original concept for the training is no longer valid

  14. Rational development of radiopharmaceuticals for HIV-1

    The global battle against HIV-1 would benefit from a sensitive and specific radiopharmaceutical to localize HIV-infected cells. Ideally, this probe would be able to identify latently infected host cells containing replication competent HIV sequences. Clinical and research applications would include assessment of reservoirs, informing clinical management by facilitating assessment of burden of infection in different compartments, monitoring disease progression and monitoring response to therapy. A “rational” development approach could facilitate efficient identification of an appropriate targeted radiopharmaceutical. Rational development starts with understanding characteristics of the disease that can be effectively targeted and then engineering radiopharmaceuticals to hone in on an appropriate target, which in the case of HIV-1 (HIV) might be an HIV-specific product on or in the host cell, a differentially expressed gene product, an integrated DNA sequence specific enzymatic activity, part of the inflammatory response, or a combination of these. This is different from the current approach that starts with a radiopharmaceutical for a target associated with a disease, mostly from autopsy studies, without a strong rationale for the potential to impact patient care. At present, no targeted therapies are available for HIV latency, although a number of approaches are under study. Here we discuss requirements for a radiopharmaceutical useful in strategies targeting persistently infected cells. The radiopharmaceutical for HIV should be developed based on HIV biology, studied in an animal model and then in humans, and ultimately used in clinical and research settings

  15. Radiopharmaceuticals for diagnosis of inflammation

    Inflammations represent mediator-induced reactions of the hematopoetic-immunologic cell system resulting from exogenous or endogenous stimuli. On cellular level, an increased expression of inflammatory genes is followed by the release of several mediators. As inflammatory response vascular permeability increases and interstitial oedema develops. Additionally, white blood cells emigrate and several transduction cascades are activated. Radiopharmaceuticals for inflammation scintigraphy should specifically reflect one or several aspects of inflammation pathophysiology on molecular level. A group of elder tracers for this purpose comprised substances that are accumulated due to the permeability of physiological barriers. However, their property to accumulate in all processes with increased vascular permeability results in a comparably low specificity of these methods. In-vitro-labelled granulocytes were the method of choice for scintigraphic imaging of inflammation for years. Investigations with 111In-labelled granulocytes are still frequently considered as the gold standard to detect inflammation by scintigraphy. The use of antibodies or antibody fragments directed against leucocytes allowed in vivo labelling and substituted more complex techniques of in vitro labelling despite of several disadvantages. Due to the superior imaging quality of positron emission tomography, [18F]FDG-labelled leucocytes might result in a renaissance of in vitro methods. In cases of cerebral inflammation, activated microglia was visualised by its increased expression of benzodiazepin receptors. An interesting approach to differentiate between infection and sterile inflammation could be the use of bacterial gyrase inhibitors labelled with radioactive compounds. At present, specificity of this method is still controversially discussed. In search of substances to visualise inflammatory transduction cascades selectively, several chemotactic and chemokinetic cytokines, metabolites of the

  16. Radiopharmaceutical development and clinical needs

    The use of radionuclides for medical applications has continued to grow at a very rapid pace. The use of radiotracers for nuclear medicine imaging and for radiotherapy of cancer as well as certain benign disorders is firmly established as an important clinical modality. Over the past ten years, nuclear medicine has experienced an evolution towards functional studies and novel therapeutic approaches. New radionuclides are required for these applications. In the developmental stages, each new isotope has to go through a phase of careful scrutiny and evaluation, and practical concerns related to the cost of production and availability must be addressed. The development of 18 F-labeled radiopharmaceuticals has opened a completely new area of investigation. Research on bioconjugates (this term includes radiolabeled antibodies, peptides, receptor-specific and other bioactive molecules) has experienced rapid growth because of the promise of a number of these ''bioactive molecules'' to serve as selective carriers of radionuclides for tumor-associated and other specific antigens/receptors ''in vivo''. The new concept of nuclear medicine, particularly when applied to the field of oncology is directed towards the physiological mechanisms and the study of molecular disfunctions. The search for new radiopharmaceuticals thus aims at studying tumors at a tissue and molecular level. Examples of this new approach are scans utilizing the following substances: -guanethidine and noradrenaline analogues such as meta-iodo-benzyl-guanidine labeled with iodine-131 or iodine-123 aimed at targeting neuroendocrine cells and their secretory granules; -various monoclonal antibodies directed at different tumor types, both for diagnostic and therapeutic purposes. Radioimmunotherapy is considered particularly suited for treatment of tumors not easily amenable to surgery and for the treatment of small disseminated lesions; -somatostatin analogs tagged with indium-111 or more recently with Yttrium

  17. Function test of radiopharmaceutical freeze dryer

    Freeze Dryer is the main tool for radiopharmaceutical production process such as drying of radiopharmaceutical kits. To increase research and development activity of radiopharmaceutical product needs new freeze dryer type of 7948030 Freezone-Stoppering Tray Dryer to obtain high quality radiopharmaceutical dry kit. The aim of this research is ensuring freeze dryer machine can be operated well and fulfilling quality assurance programme. The working principle of freeze dryer is freeze drying process. Liquid material that originally frozen then dried with a heating process at low temperature in the vacuum freeze dryer chamber and will result phorous lyophilized product. Therefore, there are some parameters on freeze dryer operation, such as temperature, pressure, and time. They will effect on quality of radiopharmaceutical kit products. This research try for dry DTPA kit with manual or auto method for ± 31 hours following the procedure of drying DTPA kit. The results showed that freeze dryer can function properly in accordance with the specifications that with manual methods, freezing process reached -40°C and -34 °C in the auto, the drying process at 15°C and 0.050 mbar on each method, and obtain dry product of DTPA kit powder (lyophilized). (author)

  18. Technetium radiopharmaceuticals. Fundamentals, synthesis, structure, and development

    Technetium-99m radiopharmaceuticals are increasingly finding application in nuclear medicine for scintigraphic and emission tomographic imaging, morphologic description and functional testing of organs. Over 80% of the radiopharmaceuticals currently clinically used are labeled with the short-lived, metastable nuclide 99mTc, whose nuclear properties are almost optimal with regard to a low radiation exposure of the patient and an effective detection of the emitted γ quanta. 99mTcO4- can be easily prepared without the use of accelerator systems through generator columns. Most of the 99mTc radiopharmaceuticals are complexes which are synthesized by reduction of 99mTcO4- in the presence of suitable ligands. To achieve a high organ specificity, some understanding of the relationship between the structure of the diagnostic agent and its organ distribution is necessary. Structure analyses can be carried out on analogous compounds of the long-lived nuclide technetium-99g; these compounds are obtainable in weighable quantities. The development of new 99mTc radiopharmaceuticals is a challenge to coordination chemists. The syntheses, molecular structures, and applications of the most important 99mTc radiopharmaceuticals will be described in this review, and current directions and tendencies of the development will be shown. (orig.)

  19. Quality controls of radiopharmaceuticals used in nuclear medicine

    Chromatographic quality controls for Tc-99m; In-113m; I-131; Tl-201 and Ga-67 radiopharmaceuticals are described. Moreover, a chromatographic system which allows to separate different radiopharmaceuticals from In-113m is pointed out. (author)

  20. Certification of GMP is imperative necessity on radiopharmaceutical manufacturers

    The general circumstances on the conception, quality of GMP and Chinese GMP for radiopharmaceutical manufacturers are introduced briefly. It explains that certification of GMP is imperative necessity on radiopharmaceutical manufacturers

  1. Radiopharmaceutical development of radiolabelled peptides

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  2. Experience from a national quality assurance system on radiopharmaceuticals

    A national quality assurance program covering all radiopharmaceuticals used in Denmark was established in 1970. A regulatory system combining official control with a pharmacy service was developed. 15 years experience in the radiopharmaceutical area will be described. This will include a discussion on registration including the evaluation of safety and efficacy and the supply of radiopharmaceuticals. Different ways of surveying the quality of radiopharmaceuticals and results of quality control analysis will be reviewed

  3. Radiopharmaceutical potential of I-131 labelled diazepam

    In this study, diazepam is a derivative of the 1.4 benzodiazepine family that the most widely used drug as anticonvulsant agent has been labeled with I-131, as a new radiopharmaceutical and its radiopharmaceutical potential has been determined. Labeling of diazepam has been performed by iodogen method and optimum labeling conditions have been determined. Optimum reaction conditions are 1 mg for iodogen amount; 1-5 mg for diazepam amount, 15-20 minutes for reaction time and room temperature for reaction temperature. Specific activity of labeled compound was 0,15 Ci/mmol level. N-octanol/water ratio was found 1.9 for 131IDZ (131I labeled diazepam). In vivo experiments have been carried out to determine radiopharmaceutical potentials of labeled compound. Biodistribution studies on rats showed that 131IDZ have accumulated in kidneys, liver, lungs and brain tissues. Scintigraphic results taken with gamma camera on rabbits agree with biodistribution results of rats. (author)

  4. The safe and effective use of radiopharmaceuticals

    In the medical applications of radionuclides, we have to arrange effective radiation protection of patients, staff and general public, maintain high standards of pharmaceutical safety and ensure that the radiopharmaceuticals are effective in use. The influence of the 1976 Council of the European Communities Euratom Directive in producing legislation in the United Kingdom controlling medical work with radioactivity is discussed. Attention is drawn to current studies in the dosimetry of radiopharmaceuticals, and some of the problems that continue to arise in evaluating the dosimetry and possible hazards of isotopes of iodine are discussed. Developments in facilities for preparing radiopharmaceuticals in hospital laboratories are considered and a short report is given of an extensive study of quality control procedures which showed that it was difficult to justify their use as a routine on established products. (Author)

  5. Radiopharmaceutical prescription in nuclear medicine departments

    In France, radiopharmaceutical prescription is often discussed depending to which juridical structure the nuclear medicine department is belonging. According to current regulation, this prescription is an obligation in a department linked to hospital with a pharmacy department inside. But situation remains unclear for independent nuclear medicine departments where physicians are not constrained to prescribe radiopharmaceuticals. However, as radiographers and nurses are only authorized to realize theirs acts in front of a medical prescription, one prescription must be realized. Nowadays, computerized prescription tools have been developed but only for radiopharmaceutical drugs and not for medical acts. In the aim to achieve a safer patient care, the prescription regulation may be applied whatever differences between nuclear medicines departments. (authors)

  6. Use of radiopharmaceuticals for treating bone metastases

    Cancer prevalence is estimated at around 2% of the population and on average between 64-80% of patients with solid tumors develop bone metastases, being breast tumors, lung and prostate those who do more frequency. In this paper an estimate of the prevalence of bone pain from metastases, with reference to the data reported in the literature is presented. the different treatment techniques are summarized for pain management with special emphasis on Radionuclidic therapy, analyzing the different factors to consider for the selection of suitable radiopharmaceutical. cost data and cost-benefit of some radiopharmaceuticals for the purpose to take into account during their selection are provided. It is concluded that although the treatment of metastatic bone disease requires multidisciplinary therapies, Radionuclidic therapy is not sufficiently used, particularly by inadequate perception of risks and costs of radiopharmaceuticals, despite the undeniable support of its efficacy and tolerability. (author)

  7. Radiopharmaceuticals in nuclear medicine: evolution and present status

    A general overview of radiopharmaceuticals and their uses in nuclear medicine is presented. A brief history is outlined followed by the current status of the radiopharmaceuticals employed in the various branches of medicine such as neurology, cardiology, oncology, G.I. system and skeletal system. Important radiopharmaceutical preparations used in radionuclide therapy are described. (author). 58 refs., 1 tab., 2 figs

  8. Synthesis of the radiopharmaceuticals for positron emission tomography

    In this paper is shown a short overview of the biogenic positron radiopharmaceuticals production and a brief summary of some PET preparation synthesis. At the end the overview of some forward-looking positron radionuclides, which can be used for a preparation of the PET radiopharmaceuticals is said. A short review of diagnostic use of PET radiopharmaceuticals is presented (authors)

  9. Radiopharmaceuticals. Pharmaceutical products at service of nuclear medicine

    In this paper, three categories od radiopharmaceuticals are considered: ready to use, radionuclide generators and inactive kits for labelling with Tc-99m. Manufacturing methods of nuclides used for the preparation of radiopharmaceuticals are mentioned, as well as the clinical application of some radiopharmaceuticals widely used on the market

  10. In vitro test for pyrogenes in radiopharmaceuticals

    Procedure and results of determination of pyrogenic substances in radiopharmaceutical preparations by an in vitro method based on the reaction between bacterial endotoxine and Limulus Amebocyte Lysate are presented. The advantage of this method as compared to the test in experimental animals performed so far has also been analyzed and proved by the fact that it enables avoidance of introduction of radioactive materials in experimental animals and of radiation effects on the results obtained in efficiency studies. The in vitro method is a quick one and requires only small quantities of the radiopharmaceutical preparation to be examined. (author)

  11. Regulatory control of radiopharmaceuticals in Tanzania

    Full text: Millions of nuclear medicine procedures are performed each year worldwide and the demand for radioisotopes is increasing rapidly.The use of radiopharmaceuticals in Tanzania like in many other countries has also been increasing in recent years that necessitates the need for close regulatory control. Their applications in the country started in 1980's in the areas of medical diagnosis and therapy and at present only one center provides such services. This paper describes how radiopharmaceuticals are regulated (radiological point of view) from importation, their use and the management of the resulting radioactive waste. The regulatory framework for nuclear safety, radiation protection and security of radioactive materials was established following the national interest in the area of peaceful applications of nuclear technology. The regulations require that any person intending to import, export or transport any apparatus, article, plant, installation or other material or substance which is a source or intended to be used for the purposes of an undertaking involving the emission of radiation, must apply for a license from the regulatory authority.Radiopharmaceuticals are not produced in the country therefore whoever intends to import, possess and use has to obtain an authorization from the regulatory authority. Licensing requirements include the presence of: Qualified personnel to administer radiopharmaceuticals; Quality Assuarance and Quality Control Programs; Radiation protection measures including emergency planning, preparedness and response; Radioactive waste management program; Written laboratory procedures and safety guidelines. With regard to radioactive waste generated, it is a requirement that waste be managed properly for the protection of personnel, general public and the environment. While liquid wastes are diluted and disposed in a normal sewage system after reaching the respective exemption levels, solids and biological materials are

  12. Radiopharmaceuticals in China. Current status and prospects

    Jia, Hong-Mei; Liu, Bo-Li [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals

    2014-04-01

    The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for β-amyloid plaques, σ{sub 1} receptors, and dopamine D{sub 2} or D{sub 4} receptors; (2) {sup 99m}Tc- and {sup 18}F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, {sup 99m}Tc-labeled glucose derivatives, σ{sub 2} receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed. (orig.)

  13. Radiopharmaceutical quality control-Pragmatic approach

    The quality control must be considered in a practical manner. The radiopharmaceuticals are drugs. They must satisfy the quality assurance control. These products are then conform to Pharmacopeia. But sometimes the user must control some data especially radiochemical purity and pH value. On all the administered solutions four controls are compulsory: radionuclide identity, administered radioactivity, organoleptic character and pH

  14. Quality control of radiopharmaceuticals. Pt. 2

    In this article, activities of the Federal Health Office are reported: a) Dictionary-like compilations of methods for control of radiochemical impurities; b) Development of analytical separation and determination procedures as well as measuring methods for the quantification of impurities; c) Market analysis of commercially available radiopharmaceuticals. (RB)

  15. Design and Development of New Radiopharmaceuticals

    The major factors in the design of a new radiopharmaceutical for radioisotope scintigraphy are the photon energy of the radionuclide, the ability to incorporate the radionuclide insuitable chemical and biological form, the radiation dose to the patient, and the cost of production of the radiopharmaceutical. In this laboratory, the radionuclides, indium-113m and ytterbium-169, and technetium-99m, have been incorporated into a variety of radiopharmaceuticals. These include particles suitable for lung and liver studies, chelates for brain and kidney studies, and ionic forms for blood pool imaging. Studies in experimental animals and man indicate that these agents offer certain advantages over previously available radiopharmaceuticals. By providing larger numbers of photons, they permit more precise temporal and spatial resolution. The longer half-life of the tin-113 parent radionuclide from which indium-113m can be eluted makes indium-113m readily available, even at sites distant from the source of production. The tin-indium generator system need be purchased only every five months rather than weekly as in the case of the widely used molybdenum-technetium system. The ytterbium-radionuclide in the chemical form of a chelate is particularly useful as an inexpensive agent that provides high photon yields for renal and brain imaging. The rapid and complete biological excretion results in low radiation dose while the longer physical half-life greatly extends the shelf-life. (author)

  16. Safety and efficacy of radiopharmaceuticals 1987

    In this text aspects of the development of new radiopharmaceuticals are reviewed with particular reference to products of biological origin such as monoclonal antibodies and human cells. Also included in this survey are the legal aspects of the introduction of new pharmaceuticals and good radiopharmacy practice

  17. Polymers and polymeric micellles for targeting radiopharmaceuticals

    Hrubý, Martin

    Valencia: Centro de Investigación Príncipe Felipe, 2008. s. 8. [International Symposium on Polymer Therapeutics: From Laboratory to Clinical Practice /7./. 26.05.2008-28.05.2008, Valencia] R&D Projects: GA AV ČR IAA400480616 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug delivery * radiopharmaceutical * polymer Subject RIV: CD - Macromolecular Chemistry

  18. Radiopharmaceuticals in China. Current status and prospects

    The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for β-amyloid plaques, σ1 receptors, and dopamine D2 or D4 receptors; (2) 99mTc- and 18F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, 99mTc-labeled glucose derivatives, σ2 receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed. (orig.)

  19. Formation and development in control cause of radiopharmaceuticals of China

    The research and manufacture of radiopharmaceuticals in China were begun in 1961. Following that year, the control cause of radiopharmaceuticals was also begun. Through the endeavour of more than thirty years, the quality standards of radio-pharmaceuticals suitable for our country were formed, the level of quality standard gradually elevated and the drug quality assured reliably. Under the leadership of the Ministry of Public Health, a quality assurance system for radiopharmaceuticals was strengthened and perfected. This system consisted of control agencies of radiopharmaceutical which was authorized by the Ministry of Public Health and of testing departments of manufacturing units. The development of the control cause of radiopharmaceutical has strongly promoted the advances of both radiopharmaceuticals and nuclear medicine

  20. Automated radiopharmaceutical production systems for positron imaging

    This study provides information that will lead towards the widespread availability of systems for routine production of positron emitting isotopes and radiopharmaceuticals in a medical setting. The first part describes the collection, evaluation, and preparation in convenient form of the pertinent physical, engineering, and chemical data related to reaction yields and isotope production. The emphasis is on the production of the four short-lived isotopes C-11, N-13, O-15 and F-18. The second part is an assessment of radiation sources including cyclotrons, linear accelerators, and other more exotic devices. Various aspects of instrumentation including ease of installation, cost, and shielding are included. The third part of the study reviews the preparation of precursors and radiopharmaceuticals by automated chemical systems. 182 refs., 3 figs., 15 tabs

  1. Transport processes of radiopharmaceuticals and -modulators

    Radiotherapy and radiology have been indispensable components in cancer care for many years. The detection limit of small tumor foci as well as the development of radio-resistance and severe side effects towards normal tissues led to the development of strategies to improve radio-diagnostic and -therapeutic approaches by pharmaceuticals. The term 'radiopharmaceutical' has been used for drugs labeled with radioactive tracers for therapy or diagnosis. In addition, drugs have been described to sensitize tumor cells to radiotherapy (radiosensitizers) or to protect normal tissues from detrimental effects of radiation (radioprotectors). The present review summarizes recent concepts on the transport of radiopharmaceuticals, radiosensitizers, and radioprotectors in cells and tissues, e.g. by ATP-binding cassette transporters such as P-glycoprotein. Strengths and weaknesses of current strategies to improve transport-based processes are discussed

  2. A new approach to radiopharmaceutical dose assessment

    Dosimetry for bone-seeking radiopharmaceuticals relies on an accurate measurement of the activity administered, a model for uptake of the pharmaceutical, and calculations of the dose to the target organ. The authors report here a new approach to experimental assessment of the radiation dose to bone using electron paramagnetic resonance (EPR) spectrometry. Ionizing radiations interact with mineralized bone tissue (hydroxyapatite) to produce dose-dependent concentrations of long-lived paramagnetic centers. They have successfully applied the EPR technique to bone tissues of an animal treated with a radiopharmaceutical to demonstrate its sensitivity towards radiation-induced centers in the mineralized tissue. Although the EPR bone dosimetry method is invasive, it does offer the first experimental technique for measuring and mapping the tissue response to the administered radioactivity

  3. Computational chemistry and metal-based radiopharmaceuticals

    Computer-assisted techniques have found extensive use in the design of organic pharmaceuticals but have not been widely applied on metal complexes, particularly on radiopharmaceuticals. Some examples of computer generated structures of complexes of In, Ga and Tc with N, S, O and P donor ligands are referred. Besides parameters directly related with molecular geometries, molecular properties of the predicted structures, as ionic charges or dipole moments, are considered to be related with biodistribution studies. The structure of a series of oxo neutral Tc-biguanide complexes are predicted by molecular mechanics calculations, and their interactions with water molecules or peptide chains correlated with experimental data of partition coefficients and percentage of human protein binding. The results stress the interest of using molecular modelling to predict molecular properties of metal-based radiopharmaceuticals, which can be successfully correlated with results of in vitro studies. (author)

  4. Detection of sentinel nodes with radiopharmaceuticals

    Yokoyama, Kunihiko; Michigishi, Takatoshi; Kinuya, Seigo; Konishi, Shota; Nakajima, Kenichi; Tonami, Norihisa [Kanazawa Univ. (Japan). School of Medicine

    2000-10-01

    Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer ({sup 99m}Tc-labeled albumin, {sup 99m}Tc-labeled tin colloid, and {sup 99m}Tc-labeled phytic acid) and founded that the detection rate was

  5. Detection of sentinel nodes with radiopharmaceuticals

    Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer (99mTc-labeled albumin, 99mTc-labeled tin colloid, and 99mTc-labeled phytic acid) and founded that the detection rate was lowest with phytic

  6. Safety and efficacy of radiopharmaceuticals 1987

    This volume contains the full text of reviw papers of which summaries were presented at het Third European Smposium on Radiopharmacy and Radiopharmaceuticals, Elsinore, Dnmark 1. -4. May 1987. Aspects of the development of new radiopharmacuticals are reviewed here with particular reference to products of monoclonal antibodies and human cells. Also included are legal aspects of the introduction of new pharmaceuticals and good radiopharmacy practice. (author.). refs.; tabs

  7. Drug interaction with radiopharmaceuticals: a review

    Mario Bernardo-Filho; Sebastião David Santos-Filho; Egberto Gaspar de Moura; Adalgisa Ieda Maiworm; Margarida Maria de Camões Orlando; Maria Expósito Penas; Valbert Nascimento Cardoso; Luciana Camargo Bernardo; Lavínia de Carvalho Brito

    2005-01-01

    Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these r...

  8. Small Molecule Radiopharmaceuticals – A Review of Current Approaches

    Chaturvedi, Shubhra; Mishra, Anil K.

    2016-01-01

    Radiopharmaceuticals are an integral component of nuclear medicine and are widely applied in diagnostics and therapy. Though widely applied, the development of an “ideal” radiopharmaceutical can be challenging. Issues such as specificity, selectivity, sensitivity, and feasible chemistry challenge the design and synthesis of radiopharmaceuticals. Over time, strategies to address the issues have evolved by making use of new technological advances in the fields of biology and chemistry. This rev...

  9. Pitfalls and Limitations of SPECT, PET, and Therapeutic Radiopharmaceuticals.

    Ballinger, James R

    2015-09-01

    Radiopharmaceuticals are widely accepted to be a very safe class of drugs, with very few adverse reactions and unexpected biodistributions. However, problems can arise because of technical issues in manufacture or reconstitution, patient preparation, or drug administration. This review presents highlights of issues that have arisen in the newer classes of radiopharmaceuticals in the last 20 years and expands the scope of the previous report to include PET and therapeutic radiopharmaceuticals. Variations in the "quality" of the eluate of a (99)Mo/(99m)Tc generator remain a major issue. Several of the newer (99m)Tc tracers require a heating step in preparation that can also lead to unacceptably low radiochemical purity. Radiolytic breakdown can be a problem with all classes of radiopharmaceuticals. Many of the newer radiopharmaceuticals localize by receptor- or transporter-mediated processes and thus can be affected by other drugs, making patient preparation more important than ever. Therapeutic radiopharmaceuticals may require coadministration of radioprotectant regimens, such as the use of lysine-arginine infusions with radiopeptide therapy. Extravasation can have serious consequences with therapeutic radiopharmaceuticals. Adverse reactions to newer radiopharmaceuticals remain rare, though may increase because of coadministration of agents such as contrast media. However, there is known to be underreporting of minor adverse reactions. Knowledge of the pitfalls that can occur with radiopharmaceuticals is important in the interpretation of nuclear medicine images and optimal patient care. PMID:26278857

  10. Use of conventional radiopharmaceuticals in drug development

    Full text: Non beta-plus radiopharmaceuticals are routinely used to monitor therapeutic and toxic effects of drugs but still there is hesitancy in using them in drug development mainly due to the fact that most of them cannot be used to directly assess the target site for which the drug is being developed. However, they can be useful during safety, preclinical and clinical testing of new drugs to measure or monitor the pharmacodynamic effects of the drug on the tissue. Initial toxic effect of the drug can be studied in small and or large animals. Screening of multiorgan toxicity can be done in small animals while chronological studies can be done in large animals where planar or SPECT imaging can be performed. For screening, a lipophilic radioactive tracer such as 125I-HIPDM can be used to study multiorgan toxicity. The percentage uptake in various organs of the drug-treated and control animals are compared to each other and the difference is assumed to reflect the tissue response of the drug. Once such a determination is made, organ-specific radiopharmaceuticals are then used to more accurately determine the toxic effect of the candidate drug as exemplified in the use of In-111 antimyosin antibody to document cardiotoxicity of the anthracyclines (particularly adriamycin). During pre-clinical and clinical testing stages, the non beta-plus radiopharmaceutical can be used to determine the therapeutic efficacy of the candidate drug as exemplified in the use of Ga-67 citrate to monitor chemotherapeutic treatment in cancer patients. The use of non-beta plus radiopharmaceuticals in drug development offers several advantages: a) the procedure is currently being routinely used to monitor therapeutic and toxic effects of drugs; b) it is simple, repeatable and adaptable to a chronological study using the same animal when employing imaging technique; c) it can be done in human thereby avoiding the necessity of extrapolating data from animals to human. To establish the use of

  11. Management and supervision of radiopharmaceuticals in China

    Full text: Nuclear technology has been widely applied in China, in which radiopharmaceuticals is a very important field. Chinese government emphasizes radiation, medical and biological safety of radiopharmaceuticals on human while promoting its application for public health. China has established full government infrastructure and corresponding legal system for safety of radiopharmaceuticals. State Food and Drug Administration (SFDA), China Atomic Energy Authority (CAEA), Ministry of Health (MOH), State Environment Protection Administration (SEPA) and other related departments have made great endeavor to ensure the safety of radiopharmaceuticals in all stages. Main roles and responsibilities. SFDA is main safety regulatory body in this field in China, its responsibilities are, as follows: 1) To draft law and administrative regulations on drug administration and supervise their enforcement. 2) To draft law and regulations on administration of medical devices and supervise their enforcement; take charge of registration and regulation of medical devices; draft relevant national standards, draw up and revise professional standards of medical devices, manufacturing practice and supervise their implementation. 3) To be in charge of drug registration, draw up, revise and promulgate national standard of drugs; be responsible for drug reevaluation, review drugs to be withdrawn. 4) To draft and revise good practices for drug research, manufacturing, distribution and use, and supervise their implementation. 5) To control the quality of drugs and medical devices in manufacturers, distributors and medical institutions; release national quality bulletin on drugs and medical devices on a regular basis; investigate and punish illegal activities of producing and selling counterfeit and inferior drugs and medical devices in accordance with law. 6) To regulate radiopharmaceuticals and devices in accordance with law. 7) To draw up and improve qualification system for licensed

  12. Radiopharmaceuticals drug interactions: a critical review

    Ralph Santos-Oliveira

    2008-12-01

    Full Text Available Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.Os radiofármacos desempenham função crítica na medicina moderna, primariamente para fins diagnósticos, mas também no monitoramento da progressão de doenças assim como na avaliação de respostas ao tratamento. O uso da tecnologia por imagem tem crescido e conseqüentemente as prescrições de medicamentos (radiofármacos em especial com esse propósito. Este fato, aumenta o risco de interações entre medicamentos e radiofármacos. Interações que podem ter um impacto na

  13. Radiopharmaceutical production in Albania and its future

    Full text: Research and developing in the field of preparing and quality control of radiopharmaceuticals have been concentrated and continue to be at the Institute of Nuclear Physics. The Institute has a radiochemical laboratory, that possesses adequate infrastructure for research and developing including the scope of radioisotopes and radiopharmaceuticals. The radiochemical laboratory and the group of radiopharmaceuticals have izeion with our Nuclear Medical Center, but also with many research institutes in the country and abroad. Studies on the field of preparing radiopharmaceuticals in the beginning were focused on developing the adequate methods for labelling and quality controls of radiopharmaceuticals more spread used in the 70s. During this time were developed methods for labelling and quality controls of hippurane, oleic acid and rosse-bengale labelled with 131J, dermatological sources with 32P and have done attempts for preparing 131J and 32P with and carrier free from imported targets. At the beginning of the 70s for diagnostic and therapeutic porpoises of thyroid gland was used 131J as 'nuclear cocktail'. Actually for diagnoses of thyroid used 99mTc, meanwhile for therapy 131J as gelatin capsules prepared in the radiochemical laboratory of Institute of Nuclear Physics. The demand for the technetium kits and the impossibility of importing them on the large quantities that covered needs of nuclear medicine for diagnoses and extents of scope of nuclear medicine were premises for developing the technique of production the cold technetium kits. In the frame of technical izeion with IAEA a laboratory was constructed for these purposes. The laboratory fulfills requirements of GMP and has enough capacity to cover demand of nuclear medicine actually and in the future. Now it is consolidated production of such kits as MDP, DMSA, DTPA, HDPA, Pyrophosphate, Phytate, Heptagluconate, etc and continuing before long with more sensitive and complicate kits such as HMPAO

  14. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides

    Welch, M.J.

    2012-02-16

    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N{sup 4}-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the

  15. Factors and pharmaceuticals that affect the radiopharmaceuticals bio distributions

    The pattern of biodistribution of radiopharmaceuticals may be affected by various agents and therapeutical procedures, chemotherapy agents, thyroid hormones, metals, radiotherapy, surgery, anesthetic agents, dialysis other radiopharmaceutical interactions. Recommendations for the detection of altered biodistribution in patients by causes not directly related with the pathology itself was given. pathology itself was given

  16. Study on QSAR of brain radiopharmaceuticals of iodoamphetamines

    According to the Fick's law, it is assumed that brain radiopharmaceuticals can pass through Brain Blood Barrier by simple diffusion process. After investigation of parameters of fourteen iodoamphetamines, a linear relationship among initial brain uptake, partition coefficient, protein binding and molecular weight has been established. This relationship may be useful in designing new brain radiopharmaceuticals and predicting initial brain uptake

  17. Main principles of good production practices for radiopharmaceuticals

    The demands are summed up placed on personnel (qualification, in-service education, practical training), occupational hygiene and work space for the preparation of radiopharmaceuticals in hospitals, in departments of nuclear medicine. The basic instruments are listed for the preparation and testing of radiopharmaceuticals as are procedures in the preparation, testing and handling. (E.S.)

  18. Consequences of electroplated targets on radiopharmaceutical preparations

    Finn, R. D.; Tirelli, S.; Sheh, Y.; Knott, A.; Gelbard, A. S.; Larson, S. M.; Dahl, J. R.

    1991-05-01

    The staff of the cyclotron facility at Memorial Sloan-Kettering Cancer Center is involved in a comprehensive radionuclide preparation program which culminates with the formulation of numerous requested short-lived, positron-emitting radiopharmaceutical agents for clinical investigation. Both the produced radionuclide as well as the final radiolabeled compound are subjected to stringent quality control standards including assays for radiochemical and chemical purity. The subtle chemical consequences resulting from the irradiation of a nickel-plated target for 13N production serve to emphasize some of these potential technical difficulties.

  19. Radiopharmaceutical chemistry in Peking University (PKU)

    Wang Xiangyun; Wu Yonghui; Wang Yi; Liu Yuanfang [Department of Technical Physics, Peking University, Beijing (China)

    2000-03-01

    In the past 15 years our research activities covered the following four aspects: (1) Labeling of monoclonal anti-bodies (McAb) with radionuclides. Both direct and indirect labeling methods by using various radionuclides were studied. (2) Designing an synthesis of radiopharmaceuticals used for myocardial imaging. Two types of Tc compounds were intensively studies: BATOs and complexes containing [{sup 99m}Tc{identical_to}N]{sup 2+} and [{sup 99m}Tc=NAr]{sup 3+} core. (3) Synthesis and screening of boron- and gadolinium-containing compounds for use in neutron capture therapy. (4) Investigation of the coordination chemistry of Tc. (author)

  20. Radiation exposure through radiopharmaceuticals in routine diagnostics

    So far proof is lacking that nuclear medical examinations have somatic or genetic radiation effects. The radioiodine test is a category apart, on account of its involving a high radiation exposure of the relatively exposed thyroid and because it has already been carried through on many patients. Recommendations for radiation hygiene can therefore only relate to the careful ascertainment of indications (e.g. skeletal scintigraphy in pre-school children), the dosage of the activity to be applied, the choice of the collimator, minimization of the bladder dose and quality controls carried out a.o. on equipment and radiopharmaceuticals. (DG)

  1. Transport of radiopharmaceuticals under enhanced security measures

    Full text: The radiopharmaceutical industry makes million of shipments each year of both finished products and the medical radionuclides used to manufacture these drug products. These shipments are made to an from almost every member state of the IAEA. Since the events of September 11, 2001 member states have taken steps to enhance security of all dangerous goods. These well intentioned steps have often resulted in delays causing significant radioactive decay of these short half-life radionuclides. The IAEA can take a leadership role in the international regulatory community by enhancing security measures without allowing delays of critical radioactive materials shipments. (author)

  2. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Russell, J.R. [Univ. of Maryland, Baltimore, MD (United States); Stabin, M.G.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  3. Analysis of biodistribution attributes of radiopharmaceuticals by BioDOT

    An important component of radiopharmaceuticals quality evaluation is determination of biological distribution attributes by animal study. This is subjective, time consuming, and difficult to quantify. A user friendly graphical statistical analysis software (BioDOT) was developed using Visual Basic 6.0 for repeatable, objective evaluate of biological distribution attribute of radiopharmaceuticals in animal. The software measured the organs mass, organs radioactivity, radioactivity decay correction, radioactivity per gram of organs, and calculate radioactivity target to non-target ratios. Radiopharmaceuticals quality assessment by a BioDOT was used to estimate post injected biological distribution, and organs radioactivity and uniformity ratio was calculated. The software quantified percent injected dose of radiopharmaceutical in selected organs of the animal study. Total percent injected dose was quantified and correlated with the standard value of BP Pharmacopoeia. The method objectively measured distribution quality attributes of radiopharmaceuticals and generate full report in pdf format in less than 10 min per study. (author)

  4. Preparation of kits for 99Tcm radiopharmaceuticals

    This publication details preparation under Good Manufacturing Practices (GMP) of thirteen widely used 99Tcm radiopharmaceuticals and their quality assurance practices. The objective of this document is to present to those who intend to launch a kit preparation programme a set of preparation procedures and other relevant information gathered during kit production over a period of more than a decade, to serve as a good starting point. The manuals and monographs included in the document are based on the experience gained in two major centres. The publication of this material is intended to give a typical example, and not the only possible procedure for preparing the kits. Following the essentials of these kit preparation procedures, it is always possible to make alterations to the composition of the kits. The kits described here concern widely used 99Tcm radiopharmaceuticals which do not require a Single Photon Emission Computed Tomography (SPECT) camera. These examples of the ''first generation'' of kits are not very intricate to prepare. Although it is advisable to have only one agent for a given intended use, a few agents for each purpose, e.g. EHDP and MDP for bone imagining, have been included in the document so that the reader can have some flexibility in selecting a particular kit. 24 refs, 2 figs

  5. Preparation of radiopharmaceuticals labeled with gallium and indium

    This project was designed to carry out routine production of Ga-68 labeled radiopharmaceuticals for use, particularly in pulmonary studies; to continue work on the development of Ga-68 labeled radiopharmaceuticals that could be used with positron emission tomography; to evaluate indium-111 and possibly gallium-68 labeled antibodies in animal models; to continue development of new chelates and bifunctional chelates for use as radiopharmaceuticals; and to develop new approaches to the delivery of radiopharmaceuticals to the brain. We have made major advances in all of these areas. In area one, we have shown that gallium-68 radiopharmaceuticals can be produced routinely under robotic control for patient studies. This has resulted in several publications by us and by our collaborators in the Pulmonary Division at Washington University. In the second area, we have continued to study gallium-68 labeled radiopharmaceuticals and have carried out the work to allow gallium-68 labeled macroaggregated albumin to be administered to patients. This was necessary due to the fact that our previous gallium-68 particulate tracer, gallium-68 labeled microspheres could not be prepared due to the fact that the microsphere kit from 3M was removed from the market. In the area of labeled antibodies we have studied indium-111 labeled antibodies in two animal models and compared gallium-68 labeled antibodies with indium and iodine antibodies in one of these models. It appears that gallium-68 labeled antibody fragments may have promise as radiopharmaceuticals

  6. Breast feeding's interruption following radiopharmaceutical administration to nursing mothers

    The radiopharmaceutical administration to lactating women for therapeutic or diagnostic purpose can achieve a radiological risk to the breast feeding child due to levels of radioactivity in the breast milk. International recommendations regarding safe assumption of nursing mother after radiopharmaceutical administration were analysed. We examined the formula proposed by Rommey et al. to establish objective guidelines in case of the administration of radiopharmaceutical to nursing mothers. The ICRP 54 metabolic model for iodine was modified in order to calculate the suppression breast feeding's period according to the radioactivity measured in the breast milk. (author). 6 refs., 1 fig., 1 tab

  7. Good Practice for Introducing Radiopharmaceuticals for Clinical Use

    The use of new radiopharmaceuticals can provide extremely valuable information in the evaluation of cancer, as well as heart and brain diseases. Information that often times cannot be obtained by other means. However, there is a perceived need in many Member States for a useful reference to facilitate and expedite the introduction of radiopharmaceuticals already in clinical use in other countries. This publication intends to provide practical support for the introduction of new radiotracers, including recommendations on the necessary steps needed to facilitate and expedite the introduction of radiopharmaceuticals in clinical use, while ensuring that a safe and high quality product is administered to the patient at all times

  8. Use of radiopharmaceuticals in Finland in 1997

    The use of radiopharmaceuticals in diagnostics and therapy has been surveyed by STUK - Radiation and Nuclear Safety Authority. In 1997 the number of nuclear medicine examinations was 51,700, and the number of treatments 2,240. In 1994 the number of nuclear medicine examinations had been 50,900, and the number of treatments 2,150. In 1997 the collective effective dose received by patients was 207 manSv, and the mean effective dose received by the population was 0.04 mSv per person. In 1994 the collective effective dose had been 220 manSv. Numbers of nuclear medicine examinations and treatments have not changed much from 1994. The collective effective dose has slightly decreased. The main reason for the reduction is decreased use of the radionuclide 131I. (orig.)

  9. Laboratory methods to evaluate therapeutic radiopharmaceuticals

    The overall aim of this coordinated research project was to develop in vivo and in vitro laboratory methods to evaluate therapeutic radiopharmaceuticals. Towards this end, the laboratory methods used in this study are described in detail. Two peptides - an 8 amino acid minigastrin analogue and octreotate - were labelled with 177Lu. Bombesin was labelled with 99mTc, and its diagnostic utility was proven. For comparison, 99mTc-TOC was used. The cell lines used in this study were AR42J cells, which overexpress somatostatin receptors found in neuroendocrine cancers, and PC3 cells, which overexpress gastric releasing peptide receptors (GRP-r) found in human prostate and breast cancers. The animal model chosen was athymic mice with implanted dorsal tumours of pathologically confirmed cell cancers. The methodology described for labelling, quality control, and in vitro and in vivo assays can be easily used with other radionuclides and other peptides of interest. (author)

  10. Manufacture of radiopharmaceuticals-recent advances

    Krieger, J.K.

    1996-12-31

    Trends in radiopharmaceutical manufacturing have been influenced by the demands of the regulatory agencies, the demands of the customers, and the ever-increasing complexity of new products. Process improvements resulting from automation in the production of radionuclides for diagnostic imaging products, {sup 99m}/Tc generators, {sup 67}Ga, and {sup 201}Tl have been introduced to enhance compliance with current good manufacturing practices and to improve worker safety, both by reducing dose in accord with as low as reasonably achievable levels of radiation and by providing an ergonomically sound environment. Tighter process control has resulted in less lot-to-lot variability and ensures reliability of supply. Reduced manufacturing lapse time for {sup 99m}Tc generators minimizes decay and conserves the supply of {sup 99}Mo. Automation has resulted in an even greater degree of remote operation and has led to reductions in dose, improved process control, and faster throughput in the manufacture of radionuclides.

  11. Good practice in the production of radiopharmaceuticals

    In the paper the evolution of concepts regarding the quality of the pharmaceutical products is analyzed in the framework of the production of radiopharmaceuticals at CENTIS. The world trends range from the quality control of the fi nal product to the comprehensive concept of quality management. It is concluded from the analysis that CENTIS has an appropriate system of Good Manufacturing Practice as a result of 15 years of systematic, growing and qualified attention to the issue, in correspondence with the world tendencies and the continuous support of CECMED, the Cuban regulatory authority. That is certified by the fact that all the production processes of CENTIS have been licensed and all the CENTIS products in the market have been registered. The existing conditions at CENTIS are favorable to establish and certificate a Quality Management System. (author)

  12. Use of radiopharmaceuticals in Finland in 1997

    Korpela, H

    1999-04-01

    The use of radiopharmaceuticals in diagnostics and therapy has been surveyed by STUK - Radiation and Nuclear Safety Authority. In 1997 the number of nuclear medicine examinations was 51,700, and the number of treatments 2,240. In 1994 the number of nuclear medicine examinations had been 50,900, and the number of treatments 2,150. In 1997 the collective effective dose received by patients was 207 manSv, and the mean effective dose received by the population was 0.04 mSv per person. In 1994 the collective effective dose had been 220 manSv. Numbers of nuclear medicine examinations and treatments have not changed much from 1994. The collective effective dose has slightly decreased. The main reason for the reduction is decreased use of the radionuclide {sup 131}I. (orig.) 4 refs.

  13. Labelling and biological evaluation of therapeutic radiopharmaceuticals

    The paper describes research aimed at developing radiolabelled agents using 'bone seeking' molecules and peptides as the target specific moieties. For the study of bone seeking molecules, hydroxyethylene diphosphonate (HEDP) and dimercaptosuccinic acid (DMSA) (V) were labelled with 188Re. For peptide radiolabelling, 99mTc and 111In were used as the diagnostic radioisotopes, and 90Y was used as the therapeutic radioisotope. The labelling yielded agents with high radiochemical purity. The labelled compounds - 188Re- HEDP, 188Re-DMSA(V), 111In-DOTATOC, 99mTc-HYNIC-TATE, 90Y-DOTATOC and 90Y-DOTATATE - were evaluated in mice, rats and healthy beagle dogs. All compounds were also tested in dogs with spontaneous tumours as pathological models. Biodistribution studies showed that the molecules accumulated in their respective target cells. Spontaneous tumours in dogs offered a unique opportunity to investigate the diagnostic utility and therapeutic behaviour of the radiopharmaceuticals. (author)

  14. Rationale and radiopharmaceuticals for myocardial imaging

    Static radionuclide imaging procedures are now available for evaluating regional myocardial perfusion and for detecting acute myocardial infarction. Thallium-201, a radiopharmaceutical which possesses many of the characteristics of potassium analogs, at present is receiving the greatest attention as a regional blood flow indicator. Ischemic lesions appear as areas of decreased tracer uptake. Unfortunately, this agent is expensive, is in limited supply and has a photopeak which is low for optimum imaging. Positive infarct images can be obtained with various technetium-99m chelates. Pyrophosphate appears to be the best of the technetium compounds studied to date although the mechanism of uptake of the chelates has not yet been fully elucidated. Therefore, quantitative measurements of infarct size are not justified. As perfusion imaging and infarct imaging provide useful, complementary data, a dual tracer approach to evaluating patients with suspected coronary artery disease and/or myocardial infarction is probably justifiable

  15. Technetium radiopharmaceuticals, current situation and perspectives

    Full text: and is still maintaining this privileged position in most departments, although the situation might change in the coming years. It owes this favourable role to its continuous availability, the convenient half-life of 6.02 h, its low radiation dose to patients and manipulators, the efficient and high resolution detection of this gamma radiation by conventional gamma cameras and the possibility to incorporate it as a transition metal in a wide variety of complexes. Most of the first-generation 99mTc-radiopharmaceuticals are structurally not well characterized (e.g. complexes of 99mTc with diphosphonates, DTPA, soluble and denatured albumin, ...) but they survive on the basis of a proven clinical usefulness. However, due to more stringent requirements with respect to manufacturing methods of labelling kits (GMP) and quality of starting matials, a tendency of discontinuation of some of these preparations has started, especially for products of biological origin or with a limited volume of sale. In the eighties and the nineties, an intensive search for new 99mTc-radiopharmaceuticals based on a rational approach (e.g. cationic complexes for myocardial perfusion agents, neutral lipophilic compounds for brain perfusion tracers, ...) and a steadily growing knowledge of Tc-complexation chemistry has resulted in efficient tracer agents for measurement of kidney function (99mTc-mertiatide), myocardial perfusion (99mTc-sestamibi, 99mTc-tetrofosmin) and brain perfusion (99mTc-exametazime, 99mTc-bicisate). In the case of the heart agents, however, the designed rational approach appeared not the correct starting idea and the successful development of the tracers was more a lucky shot. On the other hand, several similar tracer agents with appropriate characteristics for clinical use did not reach commercial availability (99mTc-ethylene dicysteine, 99mTc-NOET, 99mTc-furifosmin, 99mTc-HL-91) or were discontinued (99mTc-BATOs), mainly for reasons of economics. The intensive

  16. Procedure guideline for thyroid scintigraphy. Version 2

    The version 2 of the procedure guideline for thyroid scintigraphy is an update of the procedure guideline published in 1999. The procedure guideline considers the current amendment of legislative rules (Richtlinie Strahlenschutz in der Medizin 2002). Indication and use of radiopharmaceuticals have to be confirmed by the specialist in nuclear medicine. Activities of 75 MBq technetium-99m, respectively of 10 MBq iodine-123 should not be exceeded without an individual justification. The interpretation of the scintigraphy requires the knowledge of the patients' history, the palpation of the neck, the laboratory parameters, and of the sonography. The interpretation of the technetium-99m uptake requires the knowledge of TSH concentration. (orig.)

  17. Pattern of radiopharmaceutical administration to patients between 1982 and 1986

    Analysis of the workload of a nuclear medicine department over the period 1982 to 1986 has shown the prevalence of repeated investigations in individual patients. Records from 23 152 investigations on 17 063 patients indicated that 88.5% received a single administration and only 0.5% received more than four doses of the same radiopharmaceutical. Patterns of usage of a wide range of radiopharmaceuticals are presented and show that the technetium bone imaging agent is the radiopharmaceutical most commonly used for repeated administrations. Analysis of the radiation dose to individual patients arising from radiopharmaceutical administration has shown that only two patients in the survey exceeded 50 mSv per annum and approximately 25% of patients exceeded 5 mSv per annum. (author)

  18. Radiopharmaceutical production for PET: Quality assurance, practice, experiences and issues

    The half-lives of the positron-emitting radioisotopes, carbon-11 (t1/2 = 20.3 min) and fluorine-18 (t1/2 = 109.6 min), preclude lengthy techniques from the routine analysis of radiopharmaceuticals derived for positron emission tomography (PET). Therefore, the assurance of radiopharmaceutical quality, with respect to safety and efficacy, should rely heavily on establishing a well-defined production protocol that delivers a high quality product from materials of specified grade. Also, this protocol should be supported routinely by rapid quality control procedures. Such a combination constitutes good manufacturing practice (GMP) in radiopharmaceutical production for PET. This talk will describe the application of GMP, in a PET centre regularly producing a wide range of 11C- and 18F-radiopharmaceuticals

  19. Radionuclide production and radiopharmaceutical chemistry with BNL cyclotrons

    The Brookhaven National Laboratory (BNL) radiopharmaceutical chemistry program focuses on production and utilization of radionuclides having a half-life of > 2 hr. However, a major portion of the BNL program is devoted to short-lived radionuclides, such as 11C and 18F. Activities encompassed in the program are classified into seven areas: cyclotron parameters, radiochemistry, design and rapid synthesis of radiopharmaceuticals and labeled compounds, radiotracer evaluation in animals, studies in humans, technology transfer, and several other areas

  20. The important and clinical pharmaceutical aspects of radiopharmaceuticals usage

    Janevik-Ivanovska, Emilija; Gjorgieva, Darinka; Smilkov, Katarina

    2013-01-01

    The aim of this paper is to devote the development of new radiopharmaceuticals for nuclear medicine application and methods of quality assurance stressing the pharmaceutical aspects. Preparation, distribution, storage and use of radiopharmaceuticals involves a number of pharmaceuticals and radiation protection problems emphasized by the rapidly increasing use of this type of drug relevant for the patient, for the staff and for the environment. To study the pharmaceutical aspects of rad...

  1. Barriers to achieving commercial success for diagnostic and therapeutic radiopharmaceuticals

    The concluding session of this workshop focused on barriers that might be impeding the successful transition of radiopharmaceuticals from research tools to diagnostics and therapeutics that reach commercial success. Some lessons can be learned by reviewing the technology adoption life cycle as described by Geoffrey A. Moore (Moore, GA. Crossing the chasm. New York: HarperCollins, 2002). Additionally, a review of highly successful radiopharmaceuticals suggests that achieving commercial success may require advocacy by other interested groups

  2. Guidelines for breast feeding following maternal radiopharmaceutical administration

    A brief article examines some guidelines for breast feeding following maternal radiopharmaceutical administration. Eighteen radiopharmaceuticals are separated crudely into three categories according to their physical properties and according to their magnitude and effective half-life of excretion in breast milk, i.e. 1) breast feeding must be discontinued, 2) breast feeding must be interrupted for a short period during which milk should be expressed at normal feeding times and discarded and 3) breast feeding need not be interrupted. (UK)

  3. Preparation of radiopharmaceutical formulations; Fremstilling av radioaktive farmasoeytiske blandinger

    Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K

    1998-03-16

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially {sup 153}samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs.

  4. Application of a Small Molecule Radiopharmaceutical Concept to Improve Kinetics.

    Jeong, Jae Min

    2016-06-01

    Recently, large molecules or nanoparticles are actively studied as radiopharmaceuticals. However, their kinetics is problematic because of a slow penetration through the capillaries and slow distribution to the target. To improve the kinetics, a two-step targeting method can be applied by using small molecules and very rapid copper-free click reaction. Although this method might have limitations such as internalization of the first targeted conjugate, it will provide high target-to-non-target ratio imaging of radiopharmaceuticals. PMID:27275356

  5. Production, control and utilization of radioisotopes including radiopharmaceuticals

    From April 29th to May 5th, 1984 27 participants from 21 developing countries stayed within an IAEA Study Tour ('Production, Control and Utilization of Radioisotopes including Radiopharmaceuticals') in the GDR. In the CINR, Rossendorf the reactor, the cyclotron, the technological centre as well as the animal test laboratory were visited. The participants were made familiar by 10 papers with the development, production and control of radiopharmaceuticals in the CINR, Rossendorf. (author)

  6. Pediatric patients: criteria for radiopharmaceuticals activities in diagnostic procedures

    Recent studies recommend new criteria to determine radiopharmaceuticals activities per diagnostic procedures for children and teenagers. In USA, the criteria are: minimum and maximum activity and activity per body weight. The minimum activity is necessary for assuring the quality image due to the minimum requested statistical counting. The reduction of maximum activities minimizes the probability of detriment of radiation. In the European Union (EU), the Pediatric Dosage Card (PDC) proposes combined parameters: category of radiopharmaceutical, patient body weight and minimum activity per procedure. The PDC classifies the radiopharmaceuticals according to their biodistribution in the most sensitive organs. In Brazil, an investigation evaluated radiopharmaceuticals activities administered to 2,411 pediatric patients in sixteen institutions. The Brazilian mean activities per body weight, minimum and maximum activities used per institutions were compared with similar parameters surveyed in thirteen American hospitals. It was also used the PDC model to calculate the minimum activities per radiopharmaceuticals using recorded Brazilian patients corporal masses. The wider differences between Brazilian and USA installations were noticed for minimum activities by as much as a factor of 2 and 8. For 67Ga Citrate, the ranges of activities per patient corporal mass were by as much as a factor of 2 and 9 than activities used in USA. The range of maximum activities presented fewer differences, varying between 0.5 and 2 times for the radiopharmaceuticals studied. The present work needs the collaboration of the professional staff for discussion of the results, to promote regional surveys and to optimize pediatric patient protocols (author)

  7. Report on the Technical Meeting on Therapeutic Radiopharmaceuticals

    The purpose of the TM was to provide an experts' platform to facilitate exploring the current status and future directions on therapeutic radiopharmaceuticals. The invited talks and presentations in the TM were in the following topics: - Radionuclide Production; - Production and availability of alpha emitters and their radiopharmaceuticals; - Therapeutic radiopharmaceutical chemistry; - Targets and biological evaluation; - Medical physics and dosimetry; - Clinical applications including radioimmunotherapy and clinical needs; - Peptide receptor mediated therapy Panel discussions: - Radionuclide therapy using alpha emitters; - Regulatory challenges with therapeutic radiopharmaceuticals; - International activities in radionuclide therapy. he technical meeting generated a large interest among scientists and physicians working in the field of targeted therapy using radiopharmaceuticals. Participants from both developed and developing MS reported on recent developments on the research work and clinical studies going on in the field and provided their views on the future developments in this field. The unexpected high number of participants and the high number of presentations with exceptional quality underlines the great interest of scientists and professionals in therapeutic applications using radiolabelled drugs / biomolecules. The intensive discussions including panels specified the challenges in the future on developing novel agents and to finally use them for the benefit of patients. The IAEA can play as vital role in streamlining developments and to provide tools to overcome scientific, professional and regulatory challenges in the field of therapeutic radiopharmaceuticals

  8. Calculating patient specific doses in X-ray diagnostics and from radiopharmaceuticals

    The risk associated with exposure to ionising radiation is dependent on the characteristics of the exposed individual. The size and structure of the individual influences the absorbed dose distribution in the organs. Traditional methods used to calculate the patient organ doses are based on standardised calculation phantoms, which neglect the variance of the patient size or even sex. When estimating the radiation dose of an individual patient, patient specific calculation methods must be used. Methods for patient specific dosimetry in the fields of X-ray diagnostics and diagnostic and therapeutic use of radiopharmaceuticals were proposed in this thesis. A computer program, ODS-60, for calculating organ doses from diagnostic X-ray exposures was presented. The calculation is done in a patient specific phantom with depth dose and profile algorithms fitted to Monte Carlo simulation data from a previous study. Improvements to the version reported earlier were introduced, e.g. bone attenuation was implemented. The applicability of the program to determine patient doses from complex X-ray examinations (barium enema examination) was studied. The conversion equations derived for female and male patients as a function of patient weight gave the smallest deviation from the actual patient doses when compared to previous studies. Another computer program, Intdose, was presented for calculation of the dose distribution from radiopharmaceuticals. The calculation is based on convolution of an isotope specific point dose kernel with activity distribution, obtained from single photon emission computed tomography (SPECT) images. Anatomical information is taken from magnetic resonance (MR) or computed tomography (CT) images. According to a phantom study, Intdose agreed within 3 % with measurements. For volunteers administered diagnostic radiopharmaceuticals, the results given by Intdose were found to agree with traditional methods in cases of medium sized patients. For patients

  9. (Coordinated research of chemotherapeutic agents and radiopharmaceuticals)

    Srivastava, P.C.

    1991-01-14

    The traveler received a United Nations Development Program (UNDP) Award for Distinguished Scientists to visit Indian Research Institutions including Central Drug Research Institute (CDRI), Lucknow, the host institution, in cooperation with the Council of Scientific and Industrial Research (CSIR) of India. At CDRI, the traveler had meetings to discuss progress and future directions of on-going collaborative research work on nucleosides and had the opportunity to initiate new projects with the divisions of pharmacology, biopolymers, and membrane biology. As a part of this program, the traveler also visited Sanjay Gandhi Post Graduate Institute (SGPI) of Medical Sciences, Lucknow; Board of Radiation and Isotope Technology (BRIT) and Bhabha Atomic Research Center (BARC), Bombay; Variable Energy Cyclotron Center (VECC) and Indian Institute of Chemical Biology, Calcutta. He also attended the Indo-American Society of Nuclear Medicine Meeting held in Calcutta. The traveler delivered five seminars describing various aspects of radiopharmaceutical development at the Oak Ridge National Laboratory (ORNL) and discussed the opportunities for exchange visits to ORNL by Indian scientists.

  10. Role of radiopharmaceuticals in detection of osteomyelitis

    Osteomyelitis can present as a significant diagnostic problem in medicine. Knowledge of the presence and extent of infection involving bone is important in determining treatment. In this paper the authors review the role played by radiopharmaceutical techniques in establishing the diagnosis of osteomyelitis. Osteomyelitis has been recognized as one of the most serious complications of emergency surgery to repair severe bone trauma. It is also a complication of surgery for prosthesis placement. In still other instances, osteomyelitis can be of hematogenous origin, without a major wound site. Unlike other infections, it rarely presents with acute symptoms. Osteomyelitis is divided into two categories that are time related: acute, in which clinical signs and symptoms of bone infection have been present for less than 1 month, and chronic, in which symptoms have been present for more than 1 month. The acute type is usually caused by Staphylococcus aureus in children (often secondary to skin infection), whereas in adults it can be secondary to intravenous drug abuse. Predisposing factors such as diabetes mellitus, peripheral vascular disease, and sickle cell disease are important to the outcome of osteomyelitis. One way to determine the microbe causing the infection is direct bone biopsy from the site of suspected osteomyelitis. There is one important limitation for needle biopsy in the diagnosis of osteomyelitis. Biopsies are contraindicated in the small bones of the hands and feet, because of risk of pathologic fracture (and may be relatively contraindicated after diphosphonate therapy and loss of bone mineral)

  11. Development of radiopharmaceuticals and industrial constraints

    The development process of a diagnostic or therapeutic radiopharmaceutical does not really differ from the development of a classical drug. Some specific properties of these nuclear medicine tools mainly linked to the ease to follow their distribution in the human body allow to save a couple of years out of the dozen of years required to bring a drug on the market. Overall development costs can be significantly reduced for the same reason. An industrial who wants to invest in such a business bases its analysis on other criteria that need to evaluate the medical, safety and regulatory environment at the time of drug launching. Competition is obviously a major decision criteria, but in order to evaluate the market potential, other data must be available such as the analysis of the medical landscape, the reimbursement issues, the technology evolution, the investment needs or the development of other imaging modalities, among others. In fact all these parameters concentrate toward a common criteria, the profitability of the project. Nuclear medicine moved from an art and crafts era towards the industrial era and hence plunged from the twentieth to the twenty first century in the economic reality with all its constraints and consequences. (author)

  12. Automation of cells of radiopharmaceuticals production

    The 67Ga is an important radiopharmaceutical used to identify inflammatory processes in chronic illnesses, diagnosis by image of tumors in soft tissues and the possibility to evaluate the result for therapeutic intervention. In the present work a module of 67Ga processing was developed with the objective to reduce the interventions in the hot cell, in order to avoid oxidation caused by metallic materials, and consuming in hoses of the peristaltic pumps, that release residues that blocked the valves used in the process. With materials such as: acrylic, PVC, PEEK e teflon and they are used vacuum as method (way) of fluid transferences instead of peristaltic pump in the majority of the procedures, with this improvements the system can make shorter the lengths of transference hoses, increasing the yield in the process with less interventions for maintenance and time exposure of the workers, guaranteeing the quality and reducing the time of the processing. using a mobile system for displacement of the processing module making in the cleanness and maintenance of the cell that works with radioactive material. Reducing the time of exposure dose of the workers in compliance with RDC-17 of ANVISA, which ruling the Good Manufacturing Practice Procedures. (author)

  13. Rhenium radioisotopes for therapeutic radiopharmaceutical development

    Rhenium-186 and rhenium-188 represent two important radioisotopes which are of interest for a variety of therapeutic applications in oncology, nuclear medicine and interventional cardiology. Rhenium-186 is directly produced in a nuclear reactor and the 90 hour half-life allows distribution to distant sites. The relatively low specific activity of rhenium-186 produced in most reactors, however, permits use of phosphonates, but limits use for labelled peptides and antibodies. Rhenium-188 has a much shorter 16.9 hour half-life which makes distribution from direct reactor production difficult. However, rhenium-188 can be obtained carrier-free from a tungsten-188/rhenium-188 generator, which has a long useful shelf-life of several months which is cost-effective, especially for developing regions. In this paper we discuss the issues associated with the production of rhenium-186- and rhenium-188 and the development and use of various radiopharmaceuticals and devices labelled with these radioisotopes for bone pain palliation, endoradiotherapy of tumours by selective catheterization and tumour therapy using radiolabelled peptides and antibodies, radionuclide synovectomy and the new field of vascular radiation therapy. (author)

  14. Drug interaction with radiopharmaceuticals: a review

    Bernardo-Filho, Mario; Santos-Filho, Sebastiao David; Moura, Egberto Gaspar de; Maiworm, Adalgisa Ieda; Bernardo, Luciana Camargo; Brito, Lavinia de Carvalho [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Orlando, Margarida Maria de Camoes [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Hospital Universitario Pedro Ernesto. Setor de Medicina Nuclear; Penas, Maria Exposito [Universidade Federal do Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Setor de Medicina Nuclear; Cardoso, Valbert Nascimento [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Lab. de Radioisotopos

    2005-10-15

    Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemo perfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.(author)

  15. Drug interaction with radiopharmaceuticals: a review

    Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemo perfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.(author)

  16. Skin contamination by radiopharmaceuticals and decontamination strategies.

    Bolzinger, M A; Bolot, C; Galy, G; Chabanel, A; Pelletier, J; Briançon, S

    2010-12-15

    The aim of the present study was to evaluate the percutaneous penetration of five common radiopharmaceuticals ((99m)Tc, (67)Ga, (125)I, (111)In and (51)Cr) and to evaluate the effect of decontamination by a detergent solution dedicated to hospital institutions for that purpose. The skin kinetic profiles were established by using the in vitro Franz cell method over 24h. The skin distribution in each skin layer was quantified after 6h exposure time and the efficacy of the detergent solution to remove radionuclides was evaluated also after 6h. The most striking result was the repartition into two classes of kinetic profiles: (125)I and (99m)Tc permeated quickly (∼60% of applied activity after 24h) while the 3 other radionuclides permeated slowly (from ∼2.75% for (67)Ga to ∼10% of applied activity for (111)In). The lag times, i.e. the time necessary to cross the skin varied from 20min for (99m)Tc to 5h for (51)Cr, which accumulated in skin compartments. Skin washings with the detergent solution were particularly efficient for this radionuclide, contrary to the others for which the washing procedure should be applied earlier. The permeation of ions was dependent on their chemical and physical forms and on their salting-in or salting-out effects (coordination state and Hofmeister series). PMID:20888404

  17. The chemistry of 99mTc-labeled radiopharmaceuticals

    The subject of the chemistry of 99mTc-radiopharmaceuticals consists of a collection of bits and pieces of information without a unifying theme. Since the initial impetus to the field of organ imaging was provided by radiochemists, nuclear chemists, and clinician-investigators, using easily prepared 99mTc-compounds from available off-the-shelf ligands, complete chemical characterization was not carried for the 99mTc-radiopharmaceuticals and their metabolites. The influx of coordination, organic, and analytic chemists and their systematic studies clarified some of the structures of these tracers, and promoted the general synthetic methods of a variety of ligands and the corresponding 99mTc-chelates as well as understanding of the nature of their metabolites. Although major developments for organ-imaging radiopharmaceuticals had been made, future studies will result in the simplified methodology of protein-labeling, fine-tuning of the currently available radiopharmaceuticals for higher organ-extraction, and replacement of expensive 123I-labeled tracers with the corresponding 99mTc-tracers. In general, the Tc-complexes are thermodynamically less stable and kinetically more labile than the corresponding Re-complexes. The well established chemistry of Re-compounds, the similarity of Tc-chemistry to that of Re compounds, and structure-activity relationships of a few classes of 99mTc-labeled compounds, may promote the development of new generation of 99mTc-labeled radiopharmaceuticals.69 references

  18. Traceability in the pharmaceutical industry: application to radiopharmaceutical production

    The development of tools to promote the traceability of the drugs in the pharmaceutical industry during all the production chain is a necessary requisite. The traceability system is applied to enable the identification of the origin, destination and exact location of the drug. Traceability optimizes the process chain, reduces errors, is a requirement for quality process, promotes safety for the user and assists in pharmacovigilance. The health regulatory agency in Brazil (ANVISA) will implement a tracking system for medicaments with RDC no. 59 of 2009, to control distribution since the producer until the patients in order to prevent the traffic and adulteration of drugs. Thus, this study discusses the importance and impact of the new traceability system proposed by ANVISA in the production and distribution of radiopharmaceuticals from the Nuclear and Energy Research Institute (IPEN-CNEN). The radiopharmaceuticals have a difference track when compared with another drug classes. In this context, this RDC would increase the price of the medicines by up to 10%, since it provides deployment of a single stamp supplied by the Mint. Considering that radiopharmaceuticals are not sold to the final consumer (patients), but only for accredited medical clinics and nuclear medicine physicians, and the transport of radiopharmaceuticals is performed by specialized companies licensed by CNEN (National Nuclear Energy Commission), the use of the stamp to ensure authenticity and prevent falsification should not be appropriated and represents and additional cost for the radiopharmaceuticals. (author)

  19. Traceability in the pharmaceutical industry: application to radiopharmaceutical production

    Zanette, Camila; Melero, Laura T.U.H.; Araujo, Elaine B. de; Mengatti, Jair; Silva, Katia S. de S., E-mail: czanette@usp.br [Instituto de Pesquisas Energeticas e Nucleares, (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The development of tools to promote the traceability of the drugs in the pharmaceutical industry during all the production chain is a necessary requisite. The traceability system is applied to enable the identification of the origin, destination and exact location of the drug. Traceability optimizes the process chain, reduces errors, is a requirement for quality process, promotes safety for the user and assists in pharmacovigilance. The health regulatory agency in Brazil (ANVISA) will implement a tracking system for medicaments with RDC no. 59 of 2009, to control distribution since the producer until the patients in order to prevent the traffic and adulteration of drugs. Thus, this study discusses the importance and impact of the new traceability system proposed by ANVISA in the production and distribution of radiopharmaceuticals from the Nuclear and Energy Research Institute (IPEN-CNEN). The radiopharmaceuticals have a difference track when compared with another drug classes. In this context, this RDC would increase the price of the medicines by up to 10%, since it provides deployment of a single stamp supplied by the Mint. Considering that radiopharmaceuticals are not sold to the final consumer (patients), but only for accredited medical clinics and nuclear medicine physicians, and the transport of radiopharmaceuticals is performed by specialized companies licensed by CNEN (National Nuclear Energy Commission), the use of the stamp to ensure authenticity and prevent falsification should not be appropriated and represents and additional cost for the radiopharmaceuticals. (author)

  20. Experience from a national quality assurance system on radiopharmaceuticals

    Safety, efficacy and uniformity are as important for radiopharmaceuticals as for other drugs. This was recognized in Denmark in the sixties and a national system established during the years 1970-74. During the 15 years of experience in radiopharmaceutical quality control the main developments in Europe have been the establishment of: A real industrial production of radiopharmaceuticals; Radiopharmacy as a professional scientific discipline; A regulatory system for radiopharmaceuticals. The main problems facing us today are: The slow developments of new radiopharmaceuticals; The risk that the period of introduction of EEC regulations in Europe may slow this down further; The need for continuous improvement of radiopharmacy in hospitals (facilities, training of personnel); Further development of the regulatory system taking into account special problems like PET, monoclonal antibodies, cell-labelling, and clinical trials. One of the remedies is international cooperation. We have worked hard on this in Europe, and we now feel we are able to cooperate also with other parts of the world that so far have been more advanced in the field

  1. Results of the quality assurance testing program for radiopharmaceuticals 1982-1983

    The Australian Radiation Laboratory conducts a Radiopharmaceutical Quality Assurance Test Programme in which radiopharmaceuticals used in nuclear medicine in Australia are tested for compliance with specifications. The results of testing during 1982 and 1983 are summarised. Overall 144 batches of 27 different types of radiopharmaceutical were tested in 1982-83. Samples failed to meet specification in 17 of the 1150 tests performed. In all, failure to meet full specification was observed in 13 different types of radiopharmaceutical. No single radiopharmaceutical was responsible for more than 2 failures. Labelling errors accounted for 6/17 failures. Most other errors were of a minor nature and were due to the product being slightly outside specified limits. Of the 17 failures, 11 were associated with imported radiopharmaceuticals (86 batches tested) and 6 were associated with locally produced radiopharmaceuticals (58 batches tested). There is thus no significant difference in the failure rate of local and imported radiopharmaceuticals

  2. Present states of radiopharmaceuticals unregistered in Japan

    Described are present states of radiopharmaceuticals (RP) registered abroad but yet unregistered in Japan, together with their clinical and basic findings, essentially aiming at their early introduction in the country. Most of RP registered and to be approved in the nearest future either by Food and Drug Administration (FDA) or European Medicines Agency (EMA) are subjected to this paper. Clinical and basic features of those RP are mainly explained about their development and registration process, clinical outcome, pharmacokinetics and safety items like adverse reactions. Unregistered RP in Japan listed in this paper include total 18 RP: for therapy; 223Ra-radium chloride, 131I-tositumomab, 153Sm-lexidronam pentasodium, 90Y-yttrium chloride: for PET; 13N-ammonia, 18F-florbetapir, -fluorocholine, -fluorodopa, -fluoride, 82Rb-rubidium chloride: and for SPECT; 99mTc-arcitumomab, -sulesomab, -fanolesomab, -besilesomab, -red blood cells, 123I-ioflupane, 111In-pentetreotide, and -capromab pendetide. As well, also listed are those RP registered abroad but not actually marketed: 99mTc-apcitide, -depreotide, -nofetumomab and 111In-satumomab pendetide: and those registered by FDA as medical devices, not as RP, 90Y-microsphere and -glass microsphere, since which are to be given in the body similarly to RP. In development of RP, economical (commercial) problems are pointed out to be a rather globally common task and it is a fact that there are RP registered in Japan alone such as 123I-iofetamine and -iomazenil, of which registration has been either abandoned or not conducted in foreign countries. (T.T.)

  3. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  4. Quality assurance of radiopharmaceuticals - specifications and test procedures

    The authors report on a Radiopharmaceutical Quality Assurance Test Programme carried out by the Australian Radiation Laboratory in which radiopharmaceuticals used in nuclear medicine in Australia are tested for compliance with specifications. Where the radiopharmaceutical is the subject of a monograph in the British Pharmacopoeia or the European Pharmacopoeia, then the specifications given in the Pharmacopoeia are adopted. In other cases the specifications given have been adopted by this Laboratory and have no legal status. In some cases test procedures described have been taken from various Pharmacopoeias or methods published in the literature. In other cases test methods described have been developed at this Laboratory. It should be noted that, unless stated otherwise, specifications listed apply at all times up until product expire

  5. Results of the quality assurance testing program for radiopharmaceuticals, 1994

    The Australian Radiation Laboratory conducts a Radiopharmaceutical Quality Assurance Test Program in which radiopharmaceuticals used in nuclear medicine in Australia are tested for compliance with specifications. Where the radiopharmaceutical is the subject of a monograph in the British Pharmacopoeia or the European Pharmacopoeia, then the specifications given in the Pharmacopoeia are adopted. In other cases the specifications quoted have been adopted by this Laboratory and have no legal status. It should be noted that unless stated otherwise, the specifications listed apply at all times up to product expiry. Radionuclidic purity has been determined at the calibration time, except for Thallous [201Tl] Chloride injection where the highest impurity level up to product expiry is quoted. Samples for testing were obtained through commercial channels. All technetium-99m cold kits were reconstituted according to the directions in the package insert using Sodium Pertechnetate[99mTc] Injection. Methods used for testing are described in the report ARL/TR093

  6. Knowledge-based automated radiopharmaceutical manufacturing for Positron Emission Tomography

    This article describes the application of basic knowledge engineering principles to the design of automated synthesis equipment for radiopharmaceuticals used in Positron Emission Tomography (PET). Before discussing knowledge programming, an overview of the development of automated radiopharmaceutical synthesis systems for PET will be presented. Since knowledge systems will rely on information obtained from machine transducers, a discussion of the uses of sensory feedback in today's automated systems follows. Next, the operation of these automated systems is contrasted to radiotracer production carried out by chemists, and the rationale for and basic concepts of knowledge-based programming are explained. Finally, a prototype knowledge-based system supporting automated radiopharmaceutical manufacturing of 18FDG at Brookhaven National Laboratory (BNL) is described using 1stClass, a commercially available PC-based expert system shell

  7. Institute of Bioinorganic and Radiopharmaceutical Chemistry. Annual report 2000

    In 2000 the Rossendorf research centre continued and further developed its basic and application-oriented research. Research at the Institute of Bioinorganic and Radiopharmaceutical Chemistry, one of five institutes in the Research Centre, was focused on radiotracers as molecular probes to make the human body biochemically transparent with regard to individual molecular reactions. In this respect the potential for diagnostic application depends on the quality and versatility of radiopharmaceutical chemistry, which is the main discipline in our Institute. Areas in which the Institute was particularly active were the design of new radiotracers, both radiometal-based and natural organic molecules, the elaboration of radiolabelling concepts and procedures and the chemical and pharmacological evaluation of new tracers. This was complemented by more clinically oriented activities in the Positron Emission Tomography Centre Rossendorf. With numerous contributions in the fields of radiopharmaceutical chemistry, tumour agents, tumour diagnosis and brain biochemistry this Annual Report will document the scientific progress made in 2000. (orig.)

  8. Molecular target in oncology. Opportunity for radiopharmaceuticals development

    Cancer is a cellular multifactorial disease, regulated by changes in phenotype characteristics, such as adhesion, invasion, migration, and tumorigenesis; genotypic status of commonly altered genes (KRAS and p53); microenvironmental conditions, such pH, oxygen and nutrient supply. All these features provide opportunities for radiopharmaceuticals development, both for diagnostic and therapy. For both applications, radiopharmaceuticals molecules can be divided in small synthetic molecules, small peptides (natural or modified), large molecules such as antibody or nanoparticles. The characteristics of those molecules and use will guide the choice of the radionuclide to be used for labeling it. In the presentation, data from literature and research ongoing in the Faculty of Medicine of the University of São Paulo/Brazil will be used for demonstrate the potential for radiopharmaceuticals development. (author)

  9. Radiopharmaceutical design using novel Re-188 imido complexes

    Several efficient new methods for synthesizing rhenium compounds containing a multiply bonded imido linkage (Re≡N-R) between the metal and organic compounds for radiopharmaceutical applications are reported. The imido linkage is stable and compatible with typical organic functional groups, and offers distinct structural and synthetic advantages over other types of linkages commonly used in radiopharmaceutical design. Syntheses of representative peptide and steroid compounds from hydrazine and phosphinimine imido precursors are described, and the preparation of a 188Re-imido complex is discussed. A promising new 188Re-radiolabeling strategy for directly synthesizing rhenium imido radiopharmaceuticals, targeted for low-capacity receptor sites relevant for cancer therapy and based on solid supported imido precursors, is presented. (orig.)

  10. Design of GMP compliance radiopharmaceutical production facility in MINT

    In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines which provide radiation safety to the staff and the surrounding environment from radioactive contamination. Since 1999, BPFK (Biro Pengawalan Farmaseutikal Kebangsaan) has used the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. In the guidelines, the pharmaceutical production facility shall be designed based on clean room environment. In order to design a radiopharmaceutical production facility, it is important to combine the concept of radiation safety and clean room to ensure that both requirements from GMP and IAEA are met. The design requirement is necessary to set up a complete radiopharmaceutical production facility, which is safe, has high production quality and complies with the Malaysian and International standards. (Author)

  11. Applications of quantitative whole body autoradiographic technique in radiopharmaceutical research

    The routine evaluation of radiopharmaceuticals involves dissecting tissue distribution studies (DTDS) and gamma or positron imaging. DTDS have the following disadvantages: since not all tissues can always be sampled, sites of radiopharmaceutical uptake may be missed and because the procedure involves weighing of dissected tissue samples, the spatial resolution of this method is low and determined by the smallest amount that can be weighed accurately. Gamma camera imaging and positron emission tomography though more comprehensive in evaluating the global distribution of a compound, have relative low spatial resolution. Whole body autoradiography of small animals has a much higher spatial resolution as compared to the above and depicts the global distribution of radiopharmaceuticals. A computer-assisted quantification method of WBARG applied to positron, beta, and gamma emitters will complement the method by producing quantitative values comparable to those obtained by dissection and direct tissue counting, with the advantages of depicting the global distribution at high spatial resolution

  12. Analytical techniques for the determination of radiochemical purity of radiopharmaceuticals prepared from kits. Part II

    The evaluation of efficacy of commercially available kits used for the preparation of radiopharmaceuticals is one aspect of the Radiation Protection Bureau's radiopharmaceutical quality control program. This report describes some of the analytical methodology employed in the program. Many of the tests can be performed rapidly and with a minimum of special equipment, thus enabling the confirmation of radiopharmaceutical purity prior to patient administration

  13. Technetium-99m radiopharmaceuticals for in vivo diagnostics

    Đokić Divna Đ.

    2005-01-01

    Full Text Available Technetiiim-99m is an ideal radionuclide with optimum decay characteristics. It can be obtained in sterile, pyrogen-free and carrier-free condition, as sodium pertechnetate (Na99mTcO4, from 99Mo/99Tc generator. Because of its six-hour physical half-life and monochromatic 140 keV photons free of -radiation, administration of small amounts of 99mTc solution is possible, without a significant radiation damage to the patient. Technetium eluted from the 99Mo/99mTc generator is in the highest oxidation form (+7. It can be used for diagnostic purposes alone, but it is often used for labeling different organic and inorganic compounds. As it is unreactive, reduction with a chemical reductant, (+1, (+3 and (+5 oxidation are necessary before use. Nowadays almost 80% of radiopharmaceuticals are based on 99mTc. Radiopharmaceuticals. Radiopharmaceuticals are radionuclides or radioactive compounds used in diagnosis and therapy of human diseases. A pharmaceutical is chosen based on its localization in the organ, or its participation in its physiological function. Radiation emitted from a radionuclide is detected by a radiation detector. The ability to incorporate available radionuclides into tracer molecules has been the main goal in developing radiopharmaceuticals. As radionuclides with nuclear characteristics used as either diagnostic or therapeutic radiopharmaceuticals, are predominantly metals, they can be designed as metal essential, whereby biological distribution is determined by coordination compound, or metal tagged, in which case the properties of the carrier molecule (ligand system determine the biological distribution. This paper reviews the development of 99mTc-radiopharmaceuticals. .

  14. Kinetic investigations of sup(99m)Tc-labelled radiopharmaceuticals

    Several radiopharmaceuticals (sup(99m)Tc-Fe-ascorbates, sup(99m)Tc-Sn-DTPA, sup(99m)Tc-Sn-ACD-citrate-complex and sup(99m)Tc-Sn-tetracyclin-HAsc-ACD-complex) for renal and tumour scintigraphy were tested in animal experiments. Also tested was sup(99m)Tc-penicillamine for scintigraphic investigations of the gallbladder and the liver. The findings suggest that the different radiopharmaceuticals have different degrees of reliability and exactness, and that some of them should be combined to achieve better diagnostic values. (GSE/AK)

  15. Indigenous capacity building in radiopharmaceuticals: Saudi Arabian experience

    Easy availability of radiopharmaceuticals is a key element in the application of radioisotopes in health care. Furthermore, creating self-sufficiency within the country and the geographical region further enhances this prospect. Manufacture of radiopharmaceutical began at King Faisal Specialist Hospital and Research Centre (KFSH and RC) in 1983 with the installation of the CS-30 (26.4 MeV) cyclotron, with the intention not only to make available the cyclotron products for the country and the geographical region, but also to establish a contemporary research programme. Consequently, a PET scanner was installed at KFSH and RC in 1995. Currently, the centre routinely produces several SPECT and PET radiopharmaceuticals supporting around 40 nuclear medicine facilities within the country and the geographical region. A key motivating and driving force has been the goal of becoming a comprehensive radiopharmaceuticals manufacturing facility and making the country self-sufficient in all its radiopharmaceutical needs. Consequently, 2000 witnessed the introduction of 131I based products for diagnosis as well as for therapy. GMP is the cornerstone of any radiopharmaceuticals manufacturing programme. The KFSH and RC is a perfect example of how this operational and guiding principle has been applied and evolved over the years, culminating in an effective quality management system (ISO 9001:2000) for manufacturing high quality radiopharmaceuticals. The programme building has been 'work in progress'. For efficient functioning, the staff must be well qualified and appropriately trained to achieve the mission of the organization. This has been achieved through selective staffing, followed by extensive on the job training, as well as didactic education, including various IAEA programmes for specific training. The year 2005 marked the beginning of an expansion of the KFSH and RC's programme entailing construction of a new building; provision of a state of the art cyclotron (30 MeV), a

  16. Stannous ion determination in99mTc - radiopharmaceutical kits

    Two simple and selective methods for determination of stannous ion in radiopharmaceutical kits are proposed. One of this permits the estimation of stannic ion. The first method used is a potentiometric tiration of Sn+2 in HCl medium using KIO3 solution under nitrogen gas and a redox platinum electrode. The second method consist of a compleximetric tiration of tin (Sn+2 and Sn+4) using EDTA standart solution at pH 5.5-5.6 without use of nitrogen gas. The employed procedures indicates that both the methods can be used for routine quantitative determination of tin in most labeled radiopharmaceuticals. (author)

  17. Recent developments in the field of 123I-radiopharmaceuticals

    Due to its advantageous nuclear physical properties iodine-123 is an excellent label for radiopharmaceuticals very well suited for measurements by γ-cameras and single-photon emission tomography. The development of 123I-radiopharmaceuticals should be based on a clear biochemical concept, reliable labelling procedures and careful pharmacokinetic studies in order to evaluate the physiological behaviour of the radioiodinated compounds being analogues of metabolic substrates. The development of 123I-labelled fatty acids and biogenic amines clearly proved the successful use of 123I for labelling compounds applied in medical diagnosis. (orig.)

  18. The transport of radiopharmaceuticals in the United States

    Among all the various uses of radioactive materials for peaceful purposes, the creation and use of radiopharmaceuticals to diagnose and treat medical ailments has probably brought the greatest benefit to humanity. The use of radionuclides in medicine has mushroomed over the past 20 years, as has the number of nuclides and procedures which are now routinely used in hospitals and clinics around the globe. Parallel to the growth in the use of radiopharmaceuticals has been the growth in shipments of these nuclides and their compounds to the locations where they are used

  19. Design of radiopharmaceuticals for monitoring gene transfer therapy

    The development of radiopharmaceuticals for monitoring gene transfer therapy with emission tomography is expected to lead to improved management of cancer by the year 2010. There are now only a few examples and approaches to the design of radiopharmaceuticals for gene transfer therapy. This paper introduces a novel concept for the monitoring of gene therapy. We present the optimisation of the labelling of recombinant human β-NGF ligands for in vitro studies prior to using 123I for SPET and 124I for PET studies. (author)

  20. Radiopharmaceutical Chemistry of Targeted Radiopharmaceutics. Synthesis of 211At-Labeled Radiopharmaceuticals at High Activities for Clinical Use

    Targeted α-particle radiotherapy is an appealing approach to cancer treatment because of the potential for delivering curative doses of radiation to tumor with minimal damage to normal tissue due to a range equivalent to only a few cell diameters. Compared with β-emitters they have significant advantages from a radiobiological perspective. The LET of 211At α-particles is more than 400 times higher than the β-particles emitted by 90Y, in addition the distance between ionizing events is almost the same as that between the two strands of DNA, yielding a high probability of creating non-repairable DNA damage. It gives the ability to kill cancer cells not compromised by hypoxia, dose rate effects or cell cycle position, enhancing their attractiveness for targeted radiotherapy. However, translation of the concept to the clinic has been slow, many obstacles had to be surmounted before clinical studies could be initiated, the first clinical evaluation of a 211At- labeled mAb was made in 2001. This study circumvents many of the challenges to entering clinical studies with 211At. But several problems were encountered in maintaining efficient labeling with escalating radiation dose of alpha-particle likely related to radiolysis. The impact of the radiolysis produced by the α-particle over the labeling chemistry is much higher in comparison with typical β-emitters due to a deposition of energy in the solvent in a highly localized manner two orders of magnitude per unit volume higher than 90Y or 131I. Due to these difficulties a comprehensive basic science study about the radiolytic effects of astatine alpha-particles over the synthesis of 211At-labeled radiopharmaceuticals was carried out. Its main goal was overcoming the problem of the synthesis of 211At-labeled radiopharmaceuticals at the high activities necessaries for therapy and also to extend the shelf life of astatine elutions. Briefly this study held several steps, the first one was to study the role of solvent

  1. Investigation of handling the radiopharmaceuticals in Japan and making of guidance to handle the radiopharmaceuticals

    The Working Group in Japanese Society of Nuclear Medicine Technology conducted the investigation of handing the radiopharmaceuticals in Japan through on/off-line questionnaire to 492 facilities in the period of Nov. 14-Dec. 22, 2009 to know the present state of radiopharmaceutical (RP) handling and to compare the data with past ones. This paper describes the questionnaire results and their analysis, and guidance to handle RP, made by the Group. The questionnaire contains 32 items concerning the system for appointment of examination, personnel's responsible work, notes given at RP administration, incidence of failure and questions to positron emission tomography (PET) facilities. Answers to the questionnaire are obtained from 184 facilities (37.4%). It is found that medical radiation technologists have responsibility in 80% or more of works like RP ordering and receiving, milking, labeling and subdivision of RP solution. The results are not so much changed from the past status (15 years ago) and decreased role of pharmacists is noted in this nuclear medicinal field, which, this paper points out, is a problem revealed by the investigation. The guidance in the title is made based on the investigation for the purpose of safe and appropriate handling of RP by concerned personnel and is to be disclosed in the web of the Society. The guidance contains specifications of the brand and general names of RP, contraindication, effect, notice at administration, pre-treatment, efficacy and general pharmacology/ pharmacokinetics, side effects and other notices; and involves 39 diagnostic agents (7-head, 3-neck, 11-chest, 11-abdomen, and 7-whole body agents labeled by 99mTc, 201Tl, 123I, 111In, 133Xe, 81mKr, 67Ga or 18F) and 4 therapeutic ones (131I, 89Sr or 90Y). (K.T.)

  2. Radiopharmaceuticals for diagnosis and therapy of cancer

    This paper addresses the utilization of three very distinct enzyme systems for imaging in oncology. The first of these is an enzyme encoded by a viral gene that is not present in non-infected mammalian cells. This enzyme is a nucleoside kinase that converts selected unnatural nucleosides to nucleotides in virus-infected or gene-transfected cells, but not in normal cells. The most commonly used viral kinase in gene therapy today is Herpes simplex virus type-1 thymidine kinase (HSV tk). The imaging applications of this gene therapy system are demonstrated using data from a murine tumour gene therapy model, with 123IVFRU as the diagnostic radiopharmaceutical. The second enzyme system is endogenous to mammalian cells, but is found in highest concentrations in tissues of neutral crest derivation. The overall biochemical pathway of interest involves the conversion of tyrosine to either dopamine (neurotransmitter pathway), or to melanin (pigmentation pathway). In this system tyrosinase is the 'branching' enzyme, converting dopa to dopaquinone, thereby averting its conversion to dopamine. With selective agents, the tracer can be trapped in this 'melanin pathway', which is particularly active in melanomas. Data on the development of radioiodinated tyrosinase substrates, based on S-cysteaminyl phenol (SCAP), a highly specific tyrosinase substrate, are presented to illustrate this concept. The final example is that of endogenous enzymes that are virtually ubiquitous in biodistribution. One class of enzymes, the reductases, are particularly active in the liver and their activity is amplified in tissues that are hypoxic. They are important in radiotherapy, where they can be utilized to bioreductively activate compounds that can restore the radiosensitivity of hypoxic cells. The 2-nitroimidazoles are of special interest because they are easily reducible by a number of reductases, a process that is made selective by the reversibility of reduction in the presence of cellular

  3. Drug interaction with radiopharmaceuticals: a review

    Mario Bernardo-Filho

    2005-10-01

    Full Text Available Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural and dietary conditions, as well as some medical procedures (invasive or non-invasive, such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.Imagens clínicas são valiosas em Ciências da Saúde e a análise e a interpretação correta das mesmas auxiliam os profissionais, como médico, fisioterapeuta, terapeuta ocupacional, na tomada de decisões e subseqüentes ações terapêuticas e/ou de reabilitação. Além das doenças outros fatores podem interferir e afetar a biodisponibilidade dos radiofármacos (radiobiocomplexos e a qualidade das imagens (SPECT e PET. Além disso, a marcação de alguns desses radiobiocomplexos com Tc-99m, como proteínas plasmáticas, leucócitos e hemácias, também pode ser modificada. Entre esses fatores, estão drogas (sintéticas e naturais e condições alimentares, assim como alguns procedimentos médicos (invasivos e não invasivos, como a radioterapia, processos cirúrgicos, pr

  4. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with technetium-99m and on the bioavailability of radiopharmaceuticals

    Gomes Maria Luisa; Oliveira Marcia B. Nunes de; Bernardo-Filho Mario

    2002-01-01

    The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR) is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with technetium-99m (99mTc) and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural conse...

  5. Comparison of national PET radiopharmaceutical regulations

    In the United States (US), the European Union (EU) and Japan, physicians frequently prescribe formulations of drugs for patient care which are not available commercially, and require compounding. In the practice of Nuclear Medicine, Positron Emission Tomography (PET) presents a unique compounding challenge in the production of PET radiopharmaceuticals (RaPh), due to the short radionuclide half-lives [F-18 (110 minutes), C-11 (20 minutes), N-13 (10 minutes) and 0-15 (2 minutes)], and the need to maintain high quality standards for human use ''drugs'', particularly intravenous formulations. As PET has progressed and the utilization of PET increases each country is developing regulations to manage cyclotron radionuclide production, compounding and quality control (QC). Production of PET radionuclides in the US is currently regulated by the Nuclear Regulatory Commission (NRC). These radionuclides are then synthetically incorporated into the final PET RaPh for subsequent patient administration. Since these 'drugs' are usually administered intravenously, the regulations for sterile compounding, or manufacturing, come under Pharmacy Practice, which for the US is the Food and Drug Administration (FDA). On receipt of a physician's order for a PET drug, pharmacists (or chemists) working under the authority and supervision of a physician, or a pharmacist working in a centralized PET Nuclear Pharmacy (licensed by an individual State), can compound the PET drug and dispense it for the patient. In 2005, the US FDA published a proposed rule in the Federal Register on Current Good Manufacturing Practice (CGMP) for PET Drug Products [1]. These regulations are intended to ensure that PET drugs meet the requirements of the FDA Modernization Act (FDAMA) regarding safety, identity, strength, quality, and purity. These regulations will be included in the Code of Federal Regulation. After the rule is published, each site will have 2 years to comply with the new regulations, and to file a

  6. Institute of Bioinorganic and Radiopharmaceutical Chemistry. Annual report 1992

    The Institute of Bioinorganic and Radiopharmaceutical Chemistry of the Rossendorf Research Center (FZR) presents its 1992 anual report in order to in form on research activities in the first year of its existence. This volume contains 27 individual reports devoted to various aspects of radiotracers for nuclear medicine. (BBR)

  7. Cyclotron targets and production technologies used for radiopharmaceuticals in NPI

    Fišer, Miroslav; Kopička, Karel; Hradilek, Pavel; Hanč, Petr; Lebeda, Ondřej; Panek, T.; Vognar, M.

    2003-01-01

    Roč. 53, č. 2 (2003), s. A737-A743. ISSN 0011-4626 R&D Projects: GA AV ČR KSK4055109 Keywords : cyclotron * radiopharmaceuticals Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 0.263, year: 2003

  8. Sixth international symposium on radiopharmaceutical chemistry: Abstracts: Final report

    The 113 abstracts are arranged under the following section headings: alkyl spiperone derivatives labeled with fluorine, synthesis of compounds labeled with positron emitters, technetium compounds, positron emitters (target design and synthesis), indium and gallium, halogens, labeled proteins and antibodies, radiopharmaceuticals for brain and SPECT, general, and receptor radioligands

  9. WIPR 2013 - Radiopharmaceuticals: from research to industry - Book of abstracts

    This workshop aims at presenting the latest progress in the field of radioimmunotherapy: radiopharmaceutical production, radiochemistry, radiolabelling, nuclear imaging and clinical applications. The presentations have been divided into 4 sessions: 1) alpha or beta radioimmunotherapy, 2) peptides or antibodies, 3) the benefits from nuclear imaging, and multimodal imaging

  10. Radiopharmaceuticals Pattern of Development and Utilisation in India

    V. K. Iya

    1990-10-01

    Full Text Available The availability of research reactors at an early stage of our Atomic Energy Programme led to developmental efforts in the field of radiopharmaceuticals. Starting with temporary laboratories for this work, a sophisticated and dedicated Radiopharmaceutical Laboratory is now installed at Vashi in New Bombay. The use of several /sup 125/I-labelled compounds like Rose-Bengal, hippuran, etc. for imaging has been replaced over the years by /sup 99m/Tc compounds; the final formulations are prepared at the hospital using generators and cold kits supplied by the Board of Radioisotope Technology. Parallel with the development of short lived generators in radiopharmaceuticals came advances in imaging and instrumentation techniques, the scanners being replaced by sophisticated gamma cameras, with capabilities for tomography and computerisation. About 40 centres in India have the modern instrumentation and equipment needed for carrying out nuclear medicine procedures. Further growth of nuclear medicine centres in the country has, however, been limited by the need to import such advanced high cost instrumentation not currently available from indigenous sources. Regarding in-vitro radiopharmaceuticals, some RIA and IRMA kits and procedures have been developed. These include assay of T/sub 3/, T/sub 4/ and TSH in the thyroid group of hormones. Kits for several other important procedures are still being imported by some large medical centres. There are over a hundred and fifty medical laboratories carrying out RIA procedures.

  11. Study of the radiopharmaceutical potential of radioiodinated phenolphtalein

    Uenak, T.; Avcibasi, U.; Yildirim, Y. [Ege Univ., Bornova, Izmir (Turkey). Faculty of Science, Dept. of Chemistry, Div. of Nuclear Chemistry; Duman, Y. [Ege Univ., Bornova, Izmir (Turkey). Faculty of Medicine, Div. of Nuclear Medicine

    2004-07-01

    Starting from this pharmaceutical property of phenolphthalein, in this study we examined the radiopharmaceutical potential of radioiodinated phenolphthalein. Phenolphthalein was radioiodinated with iodine-131 using the iodogen method which was earlier applied at our laboratory for radioiodination of different kinds of chemical compounds having at least one phenyl ring in their structures. (orig.)

  12. Production and application of radioisotopes and radiopharmaceuticals - status and prospects

    Given are the main data on the use of radioisotopes and radiopharmaceuticals for nuclear medical applications. Shown are the methods for their routine production including the results obtained in the Laboratory for Radioisotopes (Vinca Institute of Nuclear Sciences). Particular emphasis is devoted to the trends in the development of the agents suitable for specific diagnostic or therapeutic applications. (author)

  13. Quality assurance of radiopharmaceuticals-specifications and test procedures

    This report is a compilation of test methods used and specifications adopted for the Radiopharmaceutical Quality Assurance Test Programme conducted by the Australian Radiation Laboratory. In some cases test procedures described have been taken from various Pharmacopoeias or methods published in the literature. In other cases test methods have been developed at the ARL

  14. Towards a harmonized radiopharmaceutical regulatory framework in Europe

    Despite European unification regarding a common legal framework for many aspects of pharmaceutical production including industrial manufacture of pharmaceuticals, the practice of pharmacy in general, and of radiopharmacy in particular, differs substantially and are mainly regulated at the national level. Herein the authors discuss major European documents relevant for radiopharmacy practice in Europe and recent developments on the national level especially regarding the small-scale preparation of radiopharmaceuticals (R P). Issues related to marketing authorization (and exemptions from it), standards of preparation, quality requirements, regulations of clinical trials and education will be outlined. Standards for the industrial preparation of pharmaceuticals are defined in Good Manufacturing Practice (GMP), not taking into account specific requirements for the small scale, extemporaneous preparation of R P. The European Association of Nuclear Medicine EANM has published several documents based on GMP and called Good Radiopharmaceutical Practice (cGRPP) to specifically address this in an attempt to harmonize R P preparation across Europe. Clinical trials have been hampered by the introduction of directive 2001/20/E C again aimed at the marketing track of industrial production and currently a number of activities are ongoing to counterbalance this problem in radiopharmaceutical research. Additionally, the role of the European Pharmacopoeia in regulating quality requirements and the need for specific education and training in the small scale radiopharmaceutical preparation are also discussed.

  15. Harvard-MIT research program in short-lived radiopharmaceuticals

    Adelstein, S.J.

    1991-01-01

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  16. Characteristic of 99mTc-glutathione radiopharmaceutical

    Technetium-99m glutathione labelled compound is a radiopharmaceutical which is used in nuclear medicine for cancer diagnoses by imaging method. The distribution and accumulation of radiopharmaceutical in the body depend on its physicochemical and biological characteristic. Therefore, the determination of its characteristic was carried out in order to assure the successful utilization of this radiopharmaceutical. The radiochemical purity was determined with thin layer chromatography (TLC-SG) using dried acetone and 0.9% of NaCl solution as a mobile phase. The charge of 99mTc-GSH was tested by electrophoresis method and its lipophilicity (P) was obtained by determination of octanol-water partition. The plasma binding protein of this radiopharmaceutical was in-vitro investigated with precipitation method using 5% of trichloro acetic acid solution. Beside that, studies on the effect of 99mTc radioactivity to the stability of 99mTc-GSH and its stability in plasma has been in-vitro carried out. From the experiment it was obtained that 99mTc-GSH has 99.08 ± 0.26% of radiochemical purity; neutral (no charge); the lipophilicity (P) = 0.03 ± 0.002; the plasma binding protein of 30.31 ± 0.04%. Utilization of 99mTc radioactivity concentration up to 21 mCi/2 mL resulted 99mTc-GSH radiopharmaceutical which was remained stable up to 5 hours with ≥ 95% of radiochemical purity. In-vitro stability test of 99mTc-GSH in plasma indicated that in the first hour of storage, the radiochemical purity drastically decreased and until 5 hours of storage, its radiochemical purity did not change significantly, that was about 50%. (author)

  17. Radiopharmaceuticals for single-photon emission computed tomography brain imaging.

    Kung, Hank F; Kung, Mei-Ping; Choi, Seok Rye

    2003-01-01

    In the past 10 years, significant progress on the development of new brain-imaging agents for single-photon emission computed tomography has been made. Most of the new radiopharmaceuticals are designed to bind specific neurotransmitter receptor or transporter sites in the central nervous system. Most of the site-specific brain radiopharmaceuticals are labeled with (123)I. Results from imaging of benzodiazepine (gamma-aminobutyric acid) receptors by [(123)I]iomazenil are useful in identifying epileptic seizure foci and changes of this receptor in psychiatric disorders. Imaging of dopamine D2/D3 receptors ([(123)I]iodobenzamide and [(123)I]epidepride) and transporters [(123)I]CIT (2-beta-carboxymethoxy-3-beta(4-iodophenyl)tropane) and [(123)I]FP-beta-CIT (N-propyl-2-beta-carboxymethoxy-3-beta(4-iodophenyl)-nortropane has proven to be a simple but powerful tool for differential diagnosis of Parkinson's and other neurodegenerative diseases. A (99m)Tc-labeled agent, [(99m)Tc]TRODAT (technetium, 2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino] ethanethiolato(3-)]oxo-[1R-(exo-exo)]-), for imaging dopamine transporters in the brain has been successfully applied in the diagnosis of Parkinson's disease. Despite the fact that (123)I radiopharmaceuticals have been widely used in Japan and in Europe, clinical application of (123)I-labeled brain radiopharmaceuticals in the United States is limited because of the difficulties in supplying such agents. Development of (99m)Tc agents will likely extend the application of site-specific brain radiopharmaceuticals for routine applications in aiding the diagnosis and monitoring treatments of various neurologic and psychiatric disorders. PMID:12605353

  18. A simple liquid detector for radiopharmaceutical processing systems

    Sensing the presence of liquids in tubing and vessels in radiochemical processing equipment provides information important to the remote or automatic control of the production of clinical doses of radiopharmaceuticals. Although modern commercial automated radiopharmaceutical synthesis machines do not usually include liquid presence as a measured process variable, earlier more complex automated synthesis devices did; and the inclusion of such feedback can increase system reliability and simplify trouble-shooting tasks carried out by computer software or human operators. Commercial liquid level detectors are often designed for large-scale industrial processes and are therefore too large or expensive to be useful in many radiochemical hardware systems. An inexpensive miniature optical liquid detector originally by Kramer and Fuchs has been duplicated here for use in monitoring the presence of liquids in teflon tubing (1/16 in. O.D.) in an enriched oxygen-18 water recovery system

  19. Infection imaging with radiopharmaceuticals in the 21st century

    Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear Medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99 m Tc ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals nd the future direction it might take. (author)

  20. Radiopharmaceuticals as therapeutic agents in medical care and treatment

    Radiation applications in medical research, care, and treatment today are being used to help millions of patients throughout the world. In recent years, the medical community has seen a renaissance of therapeutic radiation applications, particularly of strontium-89 for metastatic bone pain. Radiopharmaceuticals used as therapeutic agents (frequently known as RPTs) are designed to deliver high doses of radiation to selected malignant sites in target organs or tissues, while minimizing the radiation doses to surrounding healthy cells. Over the past several years, several type of RPTs with special properties, including compounds for labelling monoclonal antibodies, have been used in animal and human clinical trials with promising results. The modern trend in radiopharmaceutical research for oncology is the development of RPTs that may be said to be tumour-seeking and tumour-specific. Among the promising RPTs being reported in the medical literature are rhenium-186 and samarium-153. Both can be produced in research reactors available in many countries. 2 tabs

  1. Freeware for reporting radiation dosimetry following the administration of radiopharmaceuticals

    This work describes the development of a software application for reporting patient radiation dosimetry following radiopharmaceutical administration. The resulting report may be included within the patient's medical records. The application was developed in the Visual Basic programming language. The dosimetric calculations are based on the values given by the International Commission on Radiological Protection (ICRP). The software is available in both Spanish and English and can be downloaded at no cost from (www.radiopharmacy.net). - Highlights: • Freeware for reporting radiation dosimetry of administered radiopharmaceuticals. • Printing of reports that can be included within the patient's medical records. • User-friendly and intuitive interface in both English and Spanish

  2. New technologies for production of radiopharmaceuticals and other medical preparations

    The Radioisotope Centre POLATOM belongs to the group of R and D institutions whose profile of activities comprises, besides applied research work, also manufacturing of a range of products based on implementation of the Centre's own developments. The Centre possesses considerable experience in its area of expertise: forty-six years of manufacturing of various radiation sources and radiopharmaceuticals, performing metrology and analysis of radioactive materials, which makes OBRI a unique R and D unit. The Centre is a chief manufacturer supplier of radiopharmaceuticals for nuclear medicine in Poland, and also an active exporter with a market of several tens countries. The current trends in the Centre activity assume combination of R and D work with practical application of its results for production purposes. The undertaken research topics are studied in co-operation with domestic and foreign scientific institutions. (author)

  3. Influence of radioactive contaminants on absorbed dose estimates for radiopharmaceuticals

    Several popular radiopharmaceutical products contain low levels of radioactive contaminants. These contaminants increase the radiation absorbed dose to the patient without any increased benefit and, in some cases, with a decrease in image quality. The importance of a contaminant to the radiation dosimetry picture is a function of 1) the contaminant level, 2) the physical half-life of the contaminant, 3) the organ uptake and the biological half-time of the contaminant in the various body systems, and 4) the decay mode, energy, etc. of the contaminant. The general influence of these parameters is discussed in this paper; families of curves are included that reflect the changing importance of contaminant dosimetry with respect to the primary radionuclide as a function of these variables. Several specific examples are also given of currently used radiopharmaceutical products which can contain radioactive contaminants (I-123, In-111, Tl-201, Ir-191m, Rb-82, Au-195m). 7 references, 8 figures, 4 tables

  4. Production of short-lived radiopharmaceuticals with CV-28 cyclotron

    A variable energy isochronous cyclotron CV-28 at the Physical Department of the Instituto de Engenharia Nuclear in Rio de Janeiro, Brazil, is used for radionuclide production of medical interest. The production methods of 67Ga, 77Br, 111In, 123I, 201Tb and their corresponding radiopharmaceuticals were developed. The radiopharmaceuticals 77Br-bromophenol, 77Br-rose bengal, 123I-hippuric acid, 123I-rose bengal, 111In-EDTA, 111In-DTPA and 111In-citrate were under routine production. Their labelling yields were 96%, 82%, 96%, 82%, 89+-6%, 92+-4% and 100+-25%, respectively. The labelling yield and purity were determined using thin layer and paper chromatography. Bio-distribution studies in experimental animals have shown the good quality of these compounds

  5. Fabrication of SU-8 microreactors for radiopharmaceutical production

    Zizzari, A; Arima, Valentina; Zacheo, A.; Pascali, Giancarlo; Salvadori, Piero; Perrone, E; Mangiullo, D; Rinaldi, Ross

    2011-01-01

    SU-8 is a very interesting material for the fabrication of lab-on-chip devices applied to organic synthesis because of its resistance to chemicals and solvents. Among the possible application fields of microreactor technology, radiochemistry is emerging because microfluidic apparatuses allow to perform radiosynthesis in a quicker, safer and more reliable way compared to traditional vessel-based approaches. Microreactors for synthesizing [18F]-labelled radiopharmaceuticals require the employme...

  6. Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals

    The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N2S2 and N3S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents

  7. Radiopharmaceuticals in Nuclear Medicine: Evolution and Role in Dentistry

    Vani, Chappidi; Nagalaxmi, V.; Singh, Anshul; Zardi, Faisal Taiyebali; Lalitha, CH

    2013-01-01

    NUCLEAR MEDICINE is the branch of medicine and medical imaging that uses radiation emitted by a radio-pharmaceutical to provide information about both the structure and function of organ systems within the body thereby aiding in the diagnosis and treatment of a disease. This unparalleled branch of radiology concerns with the diagnostic and therapeutic use of radionuclides. The most striking feature that distinguishes Nuclear Medicine from other Imaging Modalities is that Nuclear Medicine aids...

  8. Radiopharmaceuticals and other compounds labelled with short-lived radionuclides

    Welch, Michael J

    2013-01-01

    Radiopharmaceuticals and Other Compounds Labelled with Short-Lived Radionuclides covers through both review and contributed articles the potential applications and developments in labeling with short-lived radionuclides whose use is restricted to institutions with accelerators. The book discusses the current and potential use of generator-produced radionuclides as well as other short-lived radionuclides, and the problems of quality control of such labeled compounds. The book is useful to nuclear medicine physicians.

  9. Institute of Bioinorganic and Radiopharmaceutical Chemistry. Annual report 2001

    In 2001 the Forschungszentrum Rossendorf e.V. continued and further developed its basic and application-oriented research. Research at the Institute of Bioinorganic and Radiopharmaceutical Chemistry, one of five institutes in the Research Centre, was focused on radiotracers as molecular probes to make the human body biochemically transparent with regard to individual molecular reactions. As illustrated by the large number of contributions in this report, the Institute is predominantly engaged in the coordination chemistry and radiopharmacology of technetium and rhenium. (orig.)

  10. Improving radiopharmaceutical supply chain safety by implementing bar code technology.

    Matanza, David; Hallouard, François; Rioufol, Catherine; Fessi, Hatem; Fraysse, Marc

    2014-11-01

    The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management. PMID:25144560

  11. Adherence of radiopharmaceuticals and labeled cells to intravenous tubing

    A survey of 67 nuclear medicine departments revealed no agreement on which radiolabeled agents could be injected through intravenous lines (IVs) and which required direct venipuncture. Labeled cells and several common radiopharmaceuticals were tested for adherence to intravenous tubing. Residual activity remaining in the tubing after an adequate flush was less than 1% of the injected dose in each case. Administration of radiolabeled agents through existing IVs is an acceptable alternative to direct venipuncture in many cases

  12. Analysis of radiochemical impurities in radiopharmaceuticals. Pt. 1

    In a study of the relevant literatur analytical methods for the determination of radiochemical purity of pharmaceuticals were compiled in form of a dictionary. It contains data on studies of 71 radiopharmaceuticals and a total of 123 analyses. About half of the substances were labelled with I 131. The most frequently used investigation method was thin-layer chromatography (75 analyses), followed by paper chromatography (36 analyses), electrophoresis (10 analyses) and high-pressure liquid chromatography (2 analyses). (orig.)

  13. Freeware for reporting radiation dosimetry following the administration of radiopharmaceuticals.

    Gómez Perales, Jesús Luis; García Mendoza, Antonio

    2015-09-01

    This work describes the development of a software application for reporting patient radiation dosimetry following radiopharmaceutical administration. The resulting report may be included within the patient's medical records. The application was developed in the Visual Basic programming language. The dosimetric calculations are based on the values given by the International Commission on Radiological Protection (ICRP). The software is available in both Spanish and English and can be downloaded at no cost from www.radiopharmacy.net. PMID:26092354

  14. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Alireza Aslani; Graeme Snowdon; Dale Bailey; Geoffrey Schembri; Elizabeth Bailey; Pavlakis Nick; Paul Roach

    2015-01-01

    Objective(s): Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. Methods: All syn...

  15. Results of the quality assurance testing program for radiopharmaceuticals, 1994

    Baldas, J.; Bonnyman, J.; Ivanov, Z.; Lauder, R

    1995-08-01

    The Australian Radiation Laboratory conducts a Radiopharmaceutical Quality Assurance Test Program in which radiopharmaceuticals used in nuclear medicine in Australia are tested for compliance with specifications. Where the radiopharmaceutical is the subject of a monograph in the British Pharmacopoeia or the European Pharmacopoeia, then the specifications given in the Pharmacopoeia are adopted. In other cases the specifications quoted have been adopted by this Laboratory and have no legal status. It should be noted that unless stated otherwise, the specifications listed apply at all times up to product expiry. Radionuclidic purity has been determined at the calibration time, except for Thallous [{sup 201}Tl] Chloride injection where the highest impurity level up to product expiry is quoted. Samples for testing were obtained through commercial channels. All technetium-99m cold kits were reconstituted according to the directions in the package insert using Sodium Pertechnetate[{sup 99m}Tc] Injection. Methods used for testing are described in the report ARL/TR093 24 tabs.

  16. Recent radiopharmaceutical research at the AAEC Research Establishment

    During the past few years a large part of the radiochemical research carried out at Lucas Heights has been devoted to the synthesis of ligands capable of forming chelate complexes with technetium-99m, as part of a search for tumour-localising radiopharmaceuticals. An account is given of the synthesis and biological evaluation of a range of these compounds and of the investigation of certain biochemical and biological properties affecting the clinical application of both ligands and radiopharmaceuticals. In addition to the search for novel Tc-99m radiopharmaceuticals, major research programs on the development of Tc-99m generating systems have been in progress at Lucas Heights for several years. Work on the AAEC's Mark III Tc-99m technetium generator has been brought to a successful conclusion. A new type of Tc-99m generator, which uses an insoluble zirconium molybdate gel and provides high yields of pertechnetate by a simple elution technique, has also been developed. Studies are in progress on the osmium-iridium generator

  17. RADIOPHARMACEUTICALS FOR IMAGING OF HYPOXIC TUMORS: A REVIEW

    Chaitanya Prasad Meher

    2012-11-01

    Full Text Available Radiopharmaceuticals are drugs containing a radionuclide and are used routinely in nuclear medicine for the diagnosis and therapy of various diseases. The mechanism of localization of the radiopharmaceutical in different organs provides the clue for designing of the agent meant for a specific organ or pathway. Various agent like F-18, Cu-64/67, I-123, and Tc-99m are used as imaging of hypoxic tumors. Of these, F-18-fluoromisonidazole and I-123-iodoazomycin arabinoside (IAZA have been most widely studied clinically. Non-nitro-containing bioreductive complexes, such as the Cu-60/62/64 thiosemicarbazone ATSM and Tc-99m butylene amineoxime (BnAO or HL91, have also been evaluated. In particular, I-123-IAZA and Cu-60-ATSM have shown correlation with response to radiotherapy in preliminary clinical studies. However, more preclinical studies comparing imaging with validated invasive methods and clinical studies with outcome measures are required. Nuclear medicine is poised to play an important role in optimizing the therapy of patients with hypoxic tumors. The present review is concern with the various radiopharmaceuticals used for imaging of hypoxia.

  18. Synthesis and formulation of 99m Tc-ECD radiopharmaceutical

    Nuclear medicine is a medical specialty which uses radioactive compounds (radionuclides) for diagnostic and therapeutic purposes. 99m Tc is the more common radionuclide used in many studies in nuclear medicine because its advantages: it has a photopeak of 140 KeV and a half-life of 6 hours; it can be eluted from a Molybdenum 99 generator, so radiopharmaceuticals can be prepared on site. Ethyl cysteine dimer (ECD) labelled with reduced Technetium 99m has been purposed recently as a promising radiopharmaceutical for brain perfusion imaging 99m Tc-ECD is a lipophilic neutral complex which cross the brain blood barrier and show high brain uptake. The objective of this work was synthesize and to design a freeze dried formulation for the instant preparation of 99m Tc-ECD complex useful for brain perfusion imaging. We obtained a freeze dried stable formulation for the preparation of 99m Tc-ECD kit with a radiochemical purity higher than 90 %, which fulfills with the quality control of radiopharmaceuticals. Furthermore, we developed analytic techniques for the determination of the different chemical compounds into the lyophilized kit. (Author)

  19. Bone-seeking radiopharmaceuticals in skeletal malignancy: evolution, not revolution

    Many advanced malignancies are complicated by skeletal metastases, with attendant pain and disability. External beam radiotherapy is still the most effective treatment for isolated lesions. Bone-seeking radiopharmaceuticals were perceived as a means of delivering radiation to multiple lesions simultaneously. A wide variety of radioisotopes have been used in this endeavor, with myelosuppression being the most significant potential adverse effect. Benefits of treatment are modest, including a transient improvement in pain control and perhaps prolongation of the treatment-free period. This is best demonstrated in prostate cancer with lower responses by skeletal metastases from breast and lung cancers. However, the treatment is yet to produce any improvement in patient survival. Experimental approaches to improve treatment efficacy include combination with cytotoxic therapy, and administration earlier in the course of the disease. Bone seeking radiopharmaceuticals have been used in treatment of advanced osteosarcoma in humans and canines and achieved effective palliation. The myelosuppressive effects of these agents have been exploited in patients with multiple myeloma to assist in attaining myeloablation prior to stem cell transplantation. Development of more potent non-radiolabelled bisphosphonates and recognition of their antitumour effect against several tumours has sparked a recrudescence of interest in their use for bone metastases. Set against these developments, the role of bone-seeking radiopharmaceuticals in skeletal metastases may need to be redefined

  20. Export of radiopharmaceuticals and establishment of export base of cyclotron

    Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

  1. Unusual or unanticipated alterations in the biodistribution of radiopharmaceuticals as a result of pathologic mechanisms

    This chapter discusses radiopharmaceuticals for the following: central nervous system imaging; thyroid imaging; cardiovascular imaging; lung imaging; gastrointestinal imaging; genitourinary imaging; musculoskeletal imaging

  2. The role of high performance liquid chromatography in radiochemical/radiopharmaceutical synthesis and quality assurance

    The usefulness of HPLC in all areas of radiopharmaceutics has been demonstrated in numerous laboratories, particularly in the development of in-house radiopharmaceuticals for SPECT and PET. HPLC continues to be a powerful tool in preparation and quality assurance (QA) as illustrated in such areas as chemical and radiochemical identification; product separation and isolation; preparative scale purification; and specific activity determination. A review of established HPLC techniques in radiopharmaceutics will be presented. Examples from the literature as well as newer applications will be used in an attempt to assess and define the present-day role of HPLC in the preparation of radiochemicals and radiopharmaceuticals with emphasis on QA

  3. GMP compliant radiosynthesis of11C and18F-labeled PET radiopharmaceuticals with a modular disposable cassette system

    Hessels-Scheper, J.G.; Maarsingh, P.; Kwizera, C.; Zijlma, R.; Maas, B.; De Vries, A.M.T.; Antunes, I.F.; Lub-de Hooge, M.N.; Boersma, H.H.; Dierckx, R.A.J.O.; De Vries, E.F.J.; Luurtsema, G.; Elsinga, P.H.

    2014-01-01

    Background Many nuclear medicine departments have an extensive radiopharmaceutical portfolio. Consequently, these multiple PET radiopharmaceuticals have to be produced with the same synthesis module. An important consideration in GMP-compliant PET production is to avoid potential cross-contamination

  4. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides. Final Report

    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N4-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the oxygen

  5. Profile of MIBI Liquid Phase Radiopharmaceutical for Myocardial Imaging

    I. Daruwati

    2016-04-01

    Full Text Available The 99mTc-MIBI radiopharmaceutical has been used innuclear medicine in Indonesia for myocardial imaging. BATAN researchers have mastered the technology to manufacture MIBI as a liophylized kit. A reformulation of MIBI radiopharmaceutical has been conducted to improve the stability of the kit especially in the liquid-phase kit. Basically, radiopharmaceuticals in liquid form are not different from the dry kit. However in the manufacturing of liquid-phase kit, lyophilization process was not done. To improve the stability of liquid kit, a reformulation of the components was conducted by using two separate vials (Formulation 2 and the characteristics were compared with the one-vial formulation (Formulation 1.The MIBI Formulation 2 consists of two vials, vial A containing 0.06 mg of SnCl2 2H2O and 2.6 mg Sodium Citrate 2H2O and vial B containing 0.5 mg of [Cu(MIBI4]BF4, 1 mg of cysteine hydrochloride, and 20 mg of mannitol.The purposes of this study wereto determine the stability of two different formulations of MIBI as a liquid-phase kit, to compare theirstability in different storage condition such as in refrigerator and freezer, and to compare the ratio of activities attained between target and nontargetorgans after injection to animal model. As a diagnostic agent, MIBI was reconstituted with Technetium-99m as radionuclide tracer to 99mTc-MIBI labeled compound. The radiochemical purity of 99mTc-MIBI was determined by chromatography method using alumina thin-layer chromatography paper as the stationary phase and ethanol 95% as the mobile phase. The results showed MIBI Formulation 2 has a higher stability than Formulation 1. Formulation 2 also maintaineda 96.68%radiochemical purity under 52-day storage and attainedatarget-to-nontarget activity ratio of 8.22.

  6. Analysis of residual solvents in PET radiopharmaceuticals by GC

    The residual solvents in PET radiopharmaceuticals were analyzed by GC, which were acetonitrile, ethanol, N, N-dimethylethanolamine (DMEA), dimethylsulfoxide (DMSO). The standard curves were established with the AT-624 capillary column at GC, and the sensitivity of acetonitrile and ethanol were 0.004-0.320 g/L and 0.010-0.120 g/L respectively. The residual solvents of acetonitrile, ethanol, DMEA and DMSO in PET radio- pharmaceuticals were analyzed by GC. The linearity were 0.9994, 0.9999, 0.9997, 0.999 6 respectively. The residual of acetonitrile were (0.0313±0.0433), (0.0829±0.0668), (0.0156±0.0059), (0.0254±0.0266) g/L in 18F-FDG, 18F-FLT, 11C-CFT, 11C-PIB respectively. The residual of ethanol was (0.0505±0.00528) g/L in 18F-FDG. The residual of DMSO were (0.0331±0.0180) g/L, (0.0238±0.0100) g/L in 18F-W372 and 11C-DTBZ respectively. The residual of DMEA was (0.0348±0.0022) g/L in 11C-Choline. The survived of organic solvent in PET radiopharmaceuticals can be analyzed with GC directly. The results showed that the QC should be done in PET radiopharmaceuticals purity with semi-HPLC to avoid the high residual. (authors)

  7. Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. Pt. 4

    As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals sup(99m)Tc-DMS and 99Tc-DMS with blood serum proteins was studied. The interaction of sup(99m)Tc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins. After in vitro labelling of human sera with sup(99m)Tc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65%+-3.2% by gel-filtration chromatography; 72%+-4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7%+-6.8% and 71%+-2.3%, respectively. Distribution of sup(99m)Tc-DMS or 99TcDMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with sup(99m)Tc-DMS, while the same analysis was performed with 99Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats. The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of α2-, α1- and β1-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes. (orig.)

  8. Survey of radiopharmaceuticals used for in vivo studies in medical practice in New Zealand

    To obtain up-to-date information on numbers and types of radiopharmaceutical procedures, a survey was undertaken in the last quarter of 1983. In conjunction with this survey dosimetry data for the range of radiopharmaceutical procedures has been reviewed and extended where necessary so that effective dose equivalents could be estimated and mean genetically significant and malignancy significant doses for the population derived

  9. Stabilization of Tc-99m radiopharmaceuticals by chemical additives (NOTE)

    NADEZDA VUKICEVIC; JURIJ VUCINA

    2001-01-01

    The reliability and applicability of the preparation of the three, for nuclear medicine very important, 99mTc-radiopharmaceuticals from the inactive (technetium-cold) kit solutions were tested. Each examined commercial kit was dissolved in saline (0.9 % NaCl). The conditions of the storage of the inactive kit solutions till labeling were examined. The main problem is the stablity of the reductant stannous ions which is very difficult to predict. To stabilize and ensure a good quality of the l...

  10. In-vivo behavior of tin-radiopharmaceuticals

    2003-01-01

    Tin is an essential ingredient of most technetium-99m radiopharmaceuticals but its in-vivo distribution and long-term fate are not well understood. This work describes distribution in mice of several tin-117m labeled compounds. The results indicate that stannic-HEDTMP appears to be the best overall bone localizing agent with very low blood, muscle, kidney, or liver uptake, and its binding to bone is higher than that of tin-117m-DTPA, which make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

  11. Quality control protocols for radiodiagnosis agents and radiopharmaceuticals

    Based on the compilation of pharmacopoeia methods, literature, manuals and other information developed in our laboratory, protocols have been prepared to carry out quality controls for radiodiagnosis agents (RDA), better known as kits and RDA labelled with Tc99m. Quality control protocols cover physicochemical and biological controls. Physicochemical controls described for RDA include physical characteristics, particle size and number, pH, chemical identification, humidity, tin II; whereas biological controls include sterility, acute toxicity and bacterial endotoxin determination (LAL). Physicochemical controls described for radiopharmaceuticals labelled with Tc99m are pH and radiochemical purity; while biological distribution is described as a biological control

  12. Radio-pharmacy and radio-pharmaceutical drugs

    This document proposes the table of content of a book which aims at presenting the scientific, regulatory and technical bases for the implementation of radio-pharmacy in hospital environment. It addresses fundamental theories and notions of nuclear physics and radioactivity (production of artificial radionuclides, sensors and measurement devices, radiochemistry), radiobiology and radiation protection (biological effects of ionizing radiations, radiation protection, regulation related to the use of radionuclides by health care workers), fields of application of radio-pharmaceutical drugs (diagnosis, therapy, biological researches), and radio-pharmacy management in the hospital (design, installation, organisation and operation)

  13. Radiolanthanides as radiopharmaceuticals - current and potential applications in nuclear medicine

    Full text: The purpose of this lecture is to present the current and potential application for radiolanthanide as diagnostic and therapeutic agents in diagnosis and therapy for radiopharmaceuticals. In particular these elements offer an opportunity for new and more effective therapeutic aids, however it is critical that the method of delivery is chosen carefully so that the full potential is achieved. The choice of the appropriate chemistry is key to achieving this goal. This talk will illustrated some recent approached and also suggest some future areas worthy of research

  14. 68Ga-Based Radiopharmaceuticals: Production and Application Relationship

    Irina Velikyan

    2015-07-01

    Full Text Available The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

  15. Production And Quality Control Of Radiopharmaceutical 18F-FDG

    18F-FDG is a radiopharmaceutical for imaging diagnosis with PET/CT in Nuclear Medicine. Criteria of injection pharmaceuticals are the highest standards. So, quality assurance and quality control must be followed very strictly. The selection of the procedure for 18F-FDG has based on several criteria: high chemical efficiency, short synthesis time, toxic component free and etc. The quality control of 18F-FDG consist many fields such as: nuclear physic (nuclear purity), radiochemistry (radionuclear purity, radiochemical purity), chemistry (chemical purity), radiation measurement (half life), microbiology (pyrogen, endotoxin), etc. which is following USP, BP or EP. (author)

  16. Radiopharmaceuticals introduction to drug evaluation and dose estimation

    Williams, Lawerence E

    2010-01-01

    Nanoengineering, energized by the desire to find specific targeting agents, is leading to dramatic acceleration in novel drug design. However, in this flurry of activity, some issues may be overlooked. This is especially true in the area of determining dosage and evaluating the effects of multiple agents designed to target more than one site of metastasis. Offering the unique perspective of a medical physicist who has worked directly with cancer patients for over three decades, Radiopharmaceuticals: Introduction to Drug Evaluation and Dose Estimation starts by exploring the recent history and

  17. Quality assurance considerations related to in-house radiopharmaceutical preparations

    The Food and Drug Administration through its interpretation of the Food, Drug and Cosmetic Act with various amendments not only oversees the clinical investigation of new drugs, including short-lived radiopharmaceuticals but also monitors specific basic research protocols through the activities of the approved Radioactive Drug Research Committees. Concurrent with the technical improvements being made with positron emission tomographs is the increased availability of a variety of radiolabeled substrates possessing the unique potential to serve as indicators of in vivo alteration of biochemical processes. The syntheses of certain positron emitting radioligands with specific emphasis on the quality control procedures and current good manufacturing practices are discussed

  18. Application of NHS-MAG3 in the radiopharmaceuticals labelling

    With the rapid development of molecular nuclear medicine, N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG3) as one effective bifunctional chelator has been used to radiolabel proteins, small peptides and DNA oligonucleotides with 99Tcm. The label by the MAG3-labelling method show high labelling efficiencies and high specific activities and hold desirable stability in vitro and in vivo. The binding of the label with plasma protein is low. So many potentially useful radiopharmaceuticals for diagnosis and therapy may be produced via the NHS-MAG3 method

  19. Fabrication of sterile experimental radiopharmaceuticals: technical and regulatory requirements

    The radiopharmaceuticals devoted to the biomedical research were the object of the directive 2001/20/C.E. transposition that defined again the conditions of implementation of biomedical research using drugs at human use, whom authorization is delivered by A.f.s.s.a.p.s.. In an other hand the law 2006-686 of the 13. june 2006 ( called law T.S.N.) has modified the regulatory dispositions relative to the radiation protection norms. These new dispositions allow to the health facilities to realize their research projects without difficulties for experimental drugs supply. (N.C.)

  20. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with Technetium-99m and on the bioavailability of radiopharmaceuticals

    Gomes, Maria Luisa; Oliveira, Marcia B. Nunes de [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

    2002-09-01

    The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR) is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with Technetium-99m (99mTc) and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural consequence is a correct diagnosis. However, when it is unknown, it is undesirable and the consequences are the possibility of misdiagnosis and/or the repetition of the examination with and increase of radiation dose to the patient. The possible explanation to the appearance of DIR are radiopharmaceutical modification, alternation of the labeling efficiency of the radiopharmaceutical, modification of the target, modification of no target and/or the alteration of the binding of the radiopharmaceutical on the blood proteins. The effect of drugs on the labeling of blood elements with 99 mTc might be explained by a direct inhibition (chelating action) of the stannous and pertechnetate ions, damage induced in the plasma membrane, competition of the cited ions for the same binding sites, possible generation of reactive oxygen species that could oxidize the stannous ion and/or (v) direct oxidation of the stannous ion. In conclusion, the development of biological models to study the D IR is highly relevant. (author)

  1. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with Technetium-99m and on the bioavailability of radiopharmaceuticals

    The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR) is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with Technetium-99m (99mTc) and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural consequence is a correct diagnosis. However, when it is unknown, it is undesirable and the consequences are the possibility of misdiagnosis and/or the repetition of the examination with and increase of radiation dose to the patient. The possible explanation to the appearance of DIR are radiopharmaceutical modification, alternation of the labeling efficiency of the radiopharmaceutical, modification of the target, modification of no target and/or the alteration of the binding of the radiopharmaceutical on the blood proteins. The effect of drugs on the labeling of blood elements with 99 mTc might be explained by a direct inhibition (chelating action) of the stannous and pertechnetate ions, damage induced in the plasma membrane, competition of the cited ions for the same binding sites, possible generation of reactive oxygen species that could oxidize the stannous ion and/or (v) direct oxidation of the stannous ion. In conclusion, the development of biological models to study the D IR is highly relevant. (author)

  2. The biokinetics of alpha-particle emitting radiopharmaceuticals

    The past two decades have seen wide interest in the application of alpha-particle emitting radionuclides for targeted endoradiotherapy and a large number of compounds labeled with 211At (T1/2 7.21 h), 212Bi (T1/2 1 h) or 213Bi (T1/2 0.78 h) have been studied. Knowledge of the biokinetic behaviour of such agents is important both for their optimal clinical exploitation and for general radiological protection purposes. Animal studies of the distribution and retention of 211At compounds, including ionic astatide, substituted aromatic compounds and labelled monoclonal antibodies, have provided new information on the biochemistry of astatine. With respect the thyroid gland the uptake of the astatide ion has been shown to be very much lower than that of the iodide ion. Less information is available for 212Bi-labelled radiopharmaceuticals. The available data for both 211At and 212Bi radiopharmaceuticals are reviewed. Cautious generic biokinetic models for inorganic and simple organic compounds of 211At and 212Bi; for [211At]-, and [212Bi]-biphosphonates and for [211At]-, and [212Bi]-monoclonal antibodies, are proposed for use in general radiological protection when compound-specific data are not available. (orig.)

  3. Frequency of adverse reactions to radiopharmaceuticals in Europe

    A prospective survey was performed in 17 nuclear medicine departments during 1996 in an attempt to provide reliable data on the prevalence of adverse reactions to radiopharmaceuticals. All adverse events following radiopharmaceutical administration were recorded, irrespective of the severity or likelihood of causality, and subsequently analysed using an algorithm developed by Silberstein et al., designed to establish a cause-effect relationship. A prevalence of 11 events per 105administrations was obtained (95% confidence limits 3.3-19.2). No serious of life-threatening events were reported. This rate is slightly higher than that obtained in a larger scale study in the United States (2.3 events per 10 5administrations, 95% confidence limits 1.2-3.4). The difference may be due to the decision to include or exclude vasovagal events from the analysis, the way in which the algorithm was used and the comparative size and time scale of the two studies. The prevalence of adverse reactions is approximately 1000-fold than less that occurring with iodinated contrast media and drugs. (orig.). With 2 tabs

  4. The biokinetics of alpha-particle emitting radiopharmaceuticals

    Taylor, D.M. [School of Chemistry, Cardiff Univ., Cardiff (United Kingdom); Duffield, J.R. [Faculty of Applied Sciences, Univ. of the West of England, Bristol (United Kingdom)

    2005-07-01

    The past two decades have seen wide interest in the application of alpha-particle emitting radionuclides for targeted endoradiotherapy and a large number of compounds labeled with {sup 211}At (T{sup 1}/{sub 2} 7.21 h), {sup 212}Bi (T{sup 1}/{sub 2} 1 h) or {sup 213}Bi (T{sup 1}/{sub 2} 0.78 h) have been studied. Knowledge of the biokinetic behaviour of such agents is important both for their optimal clinical exploitation and for general radiological protection purposes. Animal studies of the distribution and retention of {sup 211}At compounds, including ionic astatide, substituted aromatic compounds and labelled monoclonal antibodies, have provided new information on the biochemistry of astatine. With respect the thyroid gland the uptake of the astatide ion has been shown to be very much lower than that of the iodide ion. Less information is available for {sup 212}Bi-labelled radiopharmaceuticals. The available data for both {sup 211}At and {sup 212}Bi radiopharmaceuticals are reviewed. Cautious generic biokinetic models for inorganic and simple organic compounds of {sup 211}At and {sup 212}Bi; for [{sup 211}At]-, and [{sup 212}Bi]-biphosphonates and for [{sup 211}At]-, and [{sup 212}Bi]-monoclonal antibodies, are proposed for use in general radiological protection when compound-specific data are not available. (orig.)

  5. Process for producing astatine-211 for radiopharmaceutical use

    A one-step chemical manipulation is described in combination with a distillation and collection process for producing At-211 comprising; a. providing a target of irradiated Bismuth coated to a predetermined thickness of a backing member, b. providing a vapor-producing still operably connected with a condenser that has a water cooled condensate collector formed of a dry silica gel mesh maintained at a temperature above the freezing point of water, and providing an effluent gas filter that is operably connected to receive effluent gas from the condenser, c. heating the target in the still at a temperature in the range of about 6300-6800C for a time period in the range of 50 to 80 minutes, to evole At-211 vapor from the target, c. providing a dry carrier gas having an oxygen concentration that is sufficient to form Bi/sub 2/O/sub 3/ thereby to essentially preclude vaporization of Bi metal, passing the carrier gas through the still to carry the At-211 vapor to the condenser, and to carry effluent from the condenser to the effluent gas filter, e. eluting At-211 from the condensate collector of the condenser with a controlled volume of eluent containing predetermined solvents that are compatible with a given desired radiopharmaceutical procedure, and f. collecting the At-211 in the controlled volume of eluent for use in the given radiopharmaceutical procedure

  6. The short-term fixation of radiopharmaceuticals in bone

    The relationship between local blood flow and bone clearance of 18 F, 32 P-P (orthophosphate), 32 P-PPi (pyrophosphate), 45 Ca, 85 Sr, 99mTc- and 113 Sn-EHDP was evaluated in the non-adult rat. During one single blood passage nearly 100% of 18 F was extracted in the femoral diaphysis, the extraction efficiency for the other radiopharmaceuticals was about 40%. Blood flow and bone clearance was higher and the extraction efficiency lower in the distal femoral epiphysis including the growth plate. The short-term bone uptake of 32 P-P was lowered considerably by the simultaneous application of inactive orthophosphate, whereas the bone uptake of 32 P-PP, was not suppressed. It is suggested that the rapid deposition of radiopharmaceuticals in bone is not caused by an ionic exchange process on crystal surfaces of already existing mineral but is due to an ionic exchange during the precipitation of calcium phosphate in the calcifying bone matrix. Only 18 F is exchanged with hydroxyl groups of already precipitated hydroxyapatite, whereas the calcium and phosphate ions in the precipitated hydroxyapatite are not further accessible to an exchange process. (orig.) 891 MG/orig. 892 MBE

  7. Radiopharmaceuticals for bone and bone-marrow imaging

    The review discusses the current status of available radiopharmaceuticals for bone and bone-marrow imaging. For skeletal imaging 99Tcsup(m)-labelled diphosphonates as a group seem to be superior to other phosphorous compounds including pyrophosphate. Of the diphosphonates, 99Tcsup(m)-labelled MDP is better than EHDP. The new compound 99Tcsup(m)-IDP shows more skeletal uptake than MDP or EHDP in patients, but requires further clinical evaluation. Bone-marrow imaging has not received as much attention as bone imaging because of the lack of suitable radiopharmaceuticals. The erythropoietic marrow can be well visualized by using iron-52, an accelerator-produced positron emitter (511 keV gamma). However, availability (short half-life) and instrumentation problems limit its use to only a few institutions with access to an accelerator. The RES cell function of the bone marrow can be demonstrated by using colloids labelled with a suitable radionuclide. However, none of the available colloids of short-lived radionuclides (99Tcsup(m) or 113Insup(m)) localize to any great extent in the marrow - their localization often being limited to 10-15% of the injected dose in normal patients. Indium-111 chloride has been claimed to be useful as an erythropoietic cell marrow imaging agent by some investigators but others have disputed this claim. At the present time, we do not have an optimal agent for bone-marrow imaging and further work in this area is warranted. (author)

  8. Technetium-99m Radiopharmaceuticals in Neurology. Chapter 6

    The ideal radioisotope for single photon emission computed tomography imaging is 99mTc, due to its physical decay characteristics, its availability through commercially available generator systems and its low cost per dose. Technetium-99m hydrophilic complexes are used to evaluate the integrity of the blood-brain barrier, while neutral and lipophilic complexes are used as brain perfusion imaging agents for determination of changes in regional cerebral blood flow in various neurological disorders. Radiopharmaceuticals that bind to central nervous system (CNS) receptors in vivo are useful for understanding the pathophysiology of a number of neurological and psychiatric disorders, their diagnosis and treatment. Nowadays, CNS receptor imaging agents are, with some exceptions, typically positron emission tomography radionuclide based radiopharmaceuticals. The reason for this is not based on principal but is rather as a result of the fact that efforts in the direction of 99mTc containing agents have not been strong or consistent enough. In the chapter, the progress made in the development of 99mTc complexes for imaging dopamine transporter, 5-HT1A receptor and amyloid plaques is presented. (author)

  9. KAERI's challenge to steady production of radioisotopes and radiopharmaceuticals

    The Korea Atomic Energy Research Institute (KAERI) is a national organization in Korea, and has been doing many research and development works in radioisotope production and applications for more than 30 years. Now KAERI regularly produces radioisotopes (I-131, Tc-99m, Ho-166) for medical use and Ir-192 for industrial use. Various I-131 labeled compounds and more than 10 kinds of Tc-99m cold kits are also produced. Our multi-purpose reactor, named HANARO, has been operative since April of 1995. HANAKO is an open tank type reactor with 30 MW thermal capacity. This reactor was designed not only for research on neutron utilization but for production of radioisotopes. KAERI intended to maximize the radioisotope production capability. For this purpose, radioisotope production facilities (RIPF) have been constructed adjacent to the HANARO reactor building. There are four banks of hot cells equipped with manipulators and some of the hot cells were installed according to the KGMP standards and with clean rooms. In reviewing our RI production plan intensively, emphasis was placed on the development of new radiopharmaceuticals, development of new radiation sources for industrial and therapeutic use, and steady production of selected radioisotopes and radiopharmaceuticals. The selected items are Ho-166 based pharmaceuticals, fission Mo-99/Tc-99m generators. solution and capsules of I-131, and Ir-192 and Co-60 for industrial use. The status and future plan of KAERI's research and development program will be introduced, and will highlight programs for steady production. (author)

  10. HPLC-MS technique for radiopharmaceuticals analysis and quality control

    Potentialities of liquid chromatography with mass spectrometric detector (MSD) were investigated with the objective of quality control of radiopharmaceuticals; 2-deoxy-2-[18F]fluoro-D-glucose (FDG) being an example. Screening of suitable MSD analytical lines is presented. Mass-spectrometric monitoring of acetonitrile-aqueous ammonium formate eluant by negatively charged FDG.HCO2- ions enables isotope analysis (specific activity) of the radiopharmaceutical at m/z 227 and 226. Kryptofix 222 provides an intense MSD signal of the positive ion associated with NH4+ at m/z 394. Expired FDG injection samples contain decomposition products from which at least one labelled by 18F and characterised by signal of negative ions at m/z 207 does not correspond to FDG fragments but to C5 decomposition products. A glucose chromatographic peak, characterised by m/z 225 negative ion is accompanied by a tail of a component giving a signal of m/z 227, which can belong to [18O]glucose; isobaric sorbitol signals were excluded but FDG-glucose association occurs in the co-elution of separation of model mixtures. The latter can actually lead to a convoluted chromatographic peak, but the absence of 18F makes this inconsistent. Quantification and validation of the FDG component analysis is under way. (author)

  11. Cyclotron targets and production technologies used for radiopharmaceuticals

    Some technical aspects of development and production of cyclotron-made radiopharmaceuticals (excluding PET) are discussed. In this field, nuclear chemistry and pharmacy are in a close contact; therefore, requirements of both should be taken into account. The principles of cyclotron targetry, separation/recovery of materials and synthesis of the active substances are given, as well as issues connected with formulation pharmaceutical forms of radioactive medical products. As the radiopharmaceuticals should fulfil the requirements for in vivo preparations, there exist a variety of demands pertaining to Good Manufacturing Practice (GMP), which is also briefly discussed. A typical production chain is presented involving the treatment of irradiated cyclotron target, choosing and validation of method for pharmacon synthesis, selection or development of necessary analytical procedures, preparing active substance according pharmaceutical standards, development of dosage form, adoption of final technology procedure and opening the clinical trial. Practical examples of real technologies based on cyclotron-made radionuclides (81Rb, 123I, 68Ge, 211At) are given. Special attention is devoted to the technology of enriched cyclotron targets. Frequently used medicinal products employing some cyclotron-produced active substances are characterised (Rb/Kr or Ge/Ga generators, 123I-labelled MIBG, OIH, MAB's and some others). The cyclotron produced radioactive implants for transluminal coronary angioplasty (radioactive stent) are introduced as an example of a medical device developed for therapeutic application. (author)

  12. International symposium on trends in radiopharmaceuticals (ISTR-2005). Book of extended synopses

    Radiopharmaceuticals, along with imaging instrumentation, are the pillars that support the edifice of clinical nuclear medicine and the former is the major driver enabling investigations of molecular phenomena for better understanding of human disease and developing effective treatments. The growth of nuclear medicine has been intimately linked to availability of new radioisotopes and the discovery of new radiopharmaceuticals. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the immense contributions of scientists from diverse disciplines such as radiochemistry, inorganic chemistry, organic chemistry, biochemistry, physiology and pharmacology. Several milestones can be cited in the trajectory of this growth, which include continuing development of a plethora of 99mTc radiopharmaceuticals, automated synthesis of 18F labelled compounds, labelled peptides for accurate mapping of metastasis and the advances in radionuclide therapy. The International Symposium on Trends in Radiopharmaceuticals, ISTR-2005, under the auspices of International Atomic Energy Agency, will provide scientists and professionals working in the field of radiopharmaceuticals and related sciences an opportunity to review the exciting developments in the field. The International Atomic Energy Agency has been organizing such Symposia on Radiopharmaceuticals since 1973 and the last one was held in Lisbon, Portugal, in 1998

  13. Limulus test for pyrogens and radiometric sterility tests on radiopharmaceuticals. Part of a coordinated programme

    Sterility testing of radiopharmaceuticals prepared at BARC were carried out using the radiometric technique (Radiometric detection of the metabolic product 14Co2). Batches of different radiopharmaceuticals were tested for pyrogen using the limulus lysate method and the results were compared with the rabbit method. The results of sterility test on 202 batches of 19 different radiopharmaceuticals show that the radiometric method can be used for sterility testing of radiopharmaceuticals labelled with 35S, 51Cr, 57Co, 59Fe, 82Br, 86Rb, sup(99m)Tc, sup(113m)In, 125I and 169Yb. The radiometric test proves to be more rapid than the conventional one for the sterility testing of such radiopharmaceuticals. Detection time is between 6-21 hours. In the case of 131I-labelled radiopharmaceuticals and in the case of chlormerodrin-Hg-203, it was found an interference due to volatile species (sup(131m)Xe in the case of 131I and some volatile mercury form in the case of chlormerodrin). In these cases it would be possible to carry out the radiometric sterility test after separation of the microorganisms from the radioactive material (by filtration). The limulus lysate method can be employed for control of various pyrogen-prone raw materials and radiopharmaceuticals. Such method is the only method at present available for detecting the low level pyrogen contamination in intrathecal injections. The limulus test is more rapid than the rabbit test

  14. Is it possible to do radiopharmaceutical quality control with a gamma camera

    All of the imaging studies in nuclear medicine start with a suitable radiopharmaceutical preparation step. In radiopharmaceutical synthesis, an organic or biochemical molecule is combined with a radioactive element to form a complex. This process is known as radiolabeling (1). In a radiopharmaceutical labeling study, it is important to realize that whether or not the radiolabeled chemical complex is in the expected radiochemical form has a vital role for all the nuclear medicine imaging processes. The common method of radiopharmaceutical quality control is the chromatographic analysis such as PC, TLC, and HPLC. In nuclear medicine practice, application of these methods is called radiopharmaceutical quality control(2). The agrement of results obtained from such chromatographic analysis methods with the criterions given in United States Pharmacopea (USP) means the regulatory permission of the use of that radiopharmaceutical in proposed applications(3). In this study separation of several labeled radiopharmaceuticals were demonstrated by using standard support materials and solvents. After dying the chromatographic support material, a gamma camera (TOSHIBA GCA-602A) was used to do radiation counting and static imaging for 2 minutes. These images, then, was divided into rectangular pieces (5 x 25 in pixel) and Region of Interest (ROI) process was applied to them. The percent labeling yields were calculated by plotting total count for each area against the number of area. It was also demonstrated that the Rf values obtained from gamma camera studies were in agreement with the Rf values obtained with classical methods

  15. Quality assessment of radiopharmaceuticals in nuclear medicine services at Northeast states, Brazil

    The radiopharmaceuticals are used in the field nuclear medicine services (NMS) as tracer in the diagnoses and treatment of many diseases. Radiopharmaceuticals used in nuclear medicine and usually have a minimum of pharmacological effect. The procedures for labelling Radiopharmaceuticals should be observed in order to minimize risks to patients, employees and individuals from the public, and to be administered in humans, must be sterile and free of pyrogens and possess elements all measures of quality controls required a conventional drug. The 'Agencia Nacional de Vigilancia Sanitaria (ANVISA)' in its 'Resolucao de Diretoria Colegiada' (RDC) No. 38 of June 4th 2008, decided that the NMS must perform quality control in the generators eluate and radiopharmaceuticals according to recommendations of manufacturers and scientific evidence accepted by ANVISA. Thus, this study proposes to evaluate the quality of the generator 99Mo-99mTc eluate and radiopharmaceuticals labeled with 99mTc used in most NMS of some states in the Northeast, in relation to radionuclide, chemical, radiochemical purity and pH and promote the inclusion of procedure for quality control of radiopharmaceuticals in routine NMS. The results show that 90% radionuclidic purity, 98.2% purity chemical and radiochemical purity of 46% and 100% of the eluates are in agreement with international pharmacopoeias; already radiopharmaceuticals showed 82.6% purity and all radiochemical pH values are also in accordance with international pharmacopoeias. Even with so many positive results, staff the majority of MNS was not able to perform the quality control of the eluates and radiopharmaceuticals. Showing the importance of implementing of quality control programs of the eluates and radiopharmaceuticals in nuclear medicine. (author)

  16. Technetium-99m nitrido radiopharmaceuticals with unprecedented biological properties

    Adriano Duatti

    2002-09-01

    Full Text Available The chemical methods for the production of technetium-99m radiopharmaceuticals containing a terminal TcºN triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc-99m complexes has provided a highly efficient tool for the design and preparation of novel classes of diagnostic agents, and a number of potentially useful radiopharmaceuticals have been discovered. In particular, nitrido technetium-99m tracers have been developed for heart perfusion imaging. In this short review, the chemical and biological properties of the neutral myocardial perfusion tracer bis(N-ethoxy, N-ethyl-dithiocarbamato nitrido Tc-99m (TcN-NOEt will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium-99m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for an ideal perfusion imaging agent.Os métodos químicos para produção de radiofármacos marcados com tecnécio-99m contendo a ligação tripla terminal TcºN foram estabelecidos há mais de uma década. Desde esta época, a química dos complexos nitridos marcados com 99mTc tem sido uma ferramenta altamente eficiente para o desenho e preparo de novas classes de agentes para diagnóstico e, foi descoberto um número de radiofarmacos potencialmente úteis. Nesta pequena revisão, as propriedades biológicas e químicas do traçador para perfusão miocárdica neutra, o bis(N-etoxi, N-etil-ditiocarbamato nitrido 99mTc (TcN-NOEt, serão resumidas junto com o preparo e avaliação biológica preliminar da primeira classe de radiofármacos nitrido monocatiônico marcado com tecnécio-99m que exibe melhores propriedades em relação à biodistribuição, mais próximas daquelas esperadas para um agente perfusor ideal para imagens.

  17. Radiopharmaceuticals for the therapy of metastatic bone pain

    Ahn, Byeong Cheol [Kyungpook National University Medicine School, Daegu (Korea, Republic of)

    2006-04-15

    Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. It occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and is complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesion. {sup 32}P, {sup 89}SrCl, {sup 153}Sm-EDTMP, {sup 188}Re/{sup 186}Re-HEDP, and {sup 177}Lu-EDTMP can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic from of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and in some studies, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article

  18. Profile of radiopharmaceutical single vial dried-kit of ciprofloxacin

    Technetium-99m (99mTc-ciprofloxacin) is used in nuclear medicine to diagnose infection by imaging method. This radiopharmaceutical is available in the dried-kit which is packed in a single vial and the preparation of 99mTc-ciprofloxacin was performed by adding 99mTc radionuclide into the dried-kit. The aim of this research was to know the profile of single vial dried-kit radiopharmaceutical of ciprofloxacin. The preparation of the dried-kit using lyophilized method has been carried out. The radiochemical purity of 99mTc-ciprofloxacin was determined by double chromatography system using Whatman I/methyl ethyl ketone and ITLC-SG with ethanol - water - ammonia (2:5:1) as a mobile phase. The stability test on 99mTc-ciprofloxacin, in-vitro stability in plasma and the stability of ciprofloxacin dried-kit were performed by determining their radiochemical purity. Studies on the effect of volume on Na99mTcO4 solution to the 99mTc-ciprofloxacin radiochemical purity, and sterility test of the dried-kit had also been carried out. The lyophilized process has made the single vial dried-kit radiopharmaceuticals sterile and vacuum. The result showed that 99mTc-ciprofloxacin contained 92.07 ± 1.39% of radiochemical purity, which was stable for 30 minutes either at room temperature (26 ± 1°C ) or at 4 ± 1°C in storage. In-vitro stability test of 99mTc-ciprofloxacin in plasma indicated that more than 90% of the radiochemical purity was still stable until 5 hours of storage. Utilization of Na99mTcO4 volume was more than 1.6 mL on the labelling of ciprofloxacin dried-kit gave less than 90 % of radiochemical purity. Studies on the stability of ciprofloxacin dried-kit showed that the kit remained stable with the radiochemical purity more than 90 % after 17 weeks of storage 4 ± 2°C . (author)

  19. Analytical techniques for the determination of radiochemical purity of radiopharmaceuticals prepared from kits. Pt. III

    The evaluation of efficacy of commercially available kits used for the preparation of radiopharmaceuticals is one aspect of the Radiation Protection Bureau's radiopharmaceutical quality control program. This report describes some of the analytical methodology employed in the program. The techniques may be of interest to hospital radiopharmacy personnel since many of the tests can be performed rapidly and with a minimum of special equipment, thus enabling the confirmation of radiopharmaceutical purity prior to patient administration. Manufacturers of kits may also be interested in learning of the analytical methods used in the assessment of their products

  20. Analysis of factors which influence the local accumulation of bone-seeking radiopharmaceuticals

    A theoretical consideration of the factors which influence the accumulation of radiopharmaceuticals in bone is presented. The avidity with which /sup 99m/Tc-Sn-pyrophosphate and 18F fluoride are adsorbed by bone crystals has been measured in vitro and the efficiency with which these radiopharmaceuticals are extracted by normal bone has been measured in vivo. It is postulated that alterations in the capillary permeability in the region of a bone lesion greatly influence the target to background ratio that can be obtained with bone seeking radiopharmaceuticals. Quantitated gamma camera studies in man are presented in support of this hypothesis

  1. Analytical techniques for the determination of radiochemical purity of radiopharmaceuticals prepared from kits

    The evaluation of efficacy of commercially available kits used for the preparation of radiopharmaceuticals is one aspect of the Radiation Protection Bureau's radiopharmaceutical quality control program. This report describes some of the analytical methodology employed in the program. The techniques may be of interest to hospital radiopharmacy personnel as many of the tests can be performed rapidly and with a minimum of special equipment, thus enabling the confirmation of radiopharmaceutical purity prior to patient administration. Manufacturers of kits may also be interested in learning of the analytical methods used in the assessment of their products. (auth)

  2. Leading safety performance indicators for resilience assessment of radiopharmaceuticals production process

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzyl guanidine is used in the diagnosis of cardiac diseases, and the fluorodeoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuro psychiatry. This paper presents a leading safety performance indicators framework to assess the resilience of radiopharmaceuticals production processes. The organizations that use resilience indicators will be able to pro actively evaluate and manage safety. (author)

  3. The other chapter of use of radiopharmaceuticals in a developing country

    Full text: Nuclear Medicine is a rapidly growing field of medicine throughout the world. Developing countries are also coming fast either with establishment of new nuclear medicine centers or expansion of its old facilities. However consistent use of radiopharmaceuticals are often hampered in a developing country due to various reasons. Bangladesh is a developing country of Asia. The country has an old history of nuclear medicine, the first nuclear medicine center being established in as back as 1962. At present the country has got a total of 18 nuclear medicine centers, 15 in government sector and 3 in the private field. There are altogether 28 gamma cameras including some of them with SPECT facilities. Nearly 50,000 nuclear scans are done annually, thyroid being contributing as major share. Besides diagnostic scan radioisotopes like I-131and P-32 are used regularly for therapeutic purpose. A good amount of radiopharmaceuticals are also used in the in vitro laboratories. However the country mainly dependent on import for supply of radioisotopes and radiopharmaceuticals to these nuclear medicine centers. The country's only 3 MW reactor at Savar meet only 20% of the total demand. Regular and constant supply of radioisotopes and radiopharmaceuticals is a big problem in giving smooth service of nuclear medicine. Often the supply is interrupted or delayed due to various factors. This causes patient suffering. At the same time the cost of the test also goes high. Sometimes the radiopharmaceuticals are not available even on demand. Needless to say some newer radiopharmaceuticals like Sm-153 EDTMP, Re-186 HEDP, Sr-89 chloride, I-131 MIBG, In-111 octreotide are so costly that we can hardly think of to use that. Use of PET tracers is still a dream to many developing countries including Bangladesh. Constant and regular supply of radiopharmaceuticals is a pre condition of smooth running of a nuclear medicine center. A nuclear medicine center cannot develop until it has the

  4. Leading safety performance indicators for resilience assessment of radiopharmaceuticals production process

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Carvalho, Paulo V.R., E-mail: grecco@ien.gov.b, E-mail: luquetti@ien.gov.b, E-mail: paulov@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Instrumentacao e Confiabilidade Humana; Vidal, Mario C.R., E-mail: mvidal@ergonomia.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEP/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia de Producao. Grupo de Ergonomia e Novas Tecnologias (GENTE)

    2011-07-01

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzyl guanidine is used in the diagnosis of cardiac diseases, and the fluorodeoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuro psychiatry. This paper presents a leading safety performance indicators framework to assess the resilience of radiopharmaceuticals production processes. The organizations that use resilience indicators will be able to pro actively evaluate and manage safety. (author)

  5. Results of the quality assurance testing program for radiopharmaceuticals 1995

    Baldas, J.; Binnyman, J.; Ivanov, Z.; Lauder, R.

    1996-07-01

    The results of the quality assurance testing conducted by the Australian Radiation Laboratory is summarised. Overall 111 batches of 27 different types of radiopharmaceuticals were tested on samples obtained through normal commercial channels. Failure to meet full specifications was observed in 10 of the 111 batches. All technetium-99m cold kits were reconstituted according to the directions in the package insert using sodium pertechnetate ( {sup 99m}Tc) injection. Radionuclidic purity has been determined at the calibration time, except for Thallous [{sup 201}Tl] Chloride injection where the highest impurity level up to product expiry is quoted. Non-compliance of the vial label was observed in one of the ten batches failing specification and was the sole cause of product failure for this batch. Vial label non-compliance consisted of, absence of volume in the vial. Six batches failed the biodistribution test but in no case did this involve failure of the distribution for the target organs. tabs.

  6. Results of the quality assurance testing program for radiopharmaceuticals 1995

    The results of the quality assurance testing conducted by the Australian Radiation Laboratory is summarised. Overall 111 batches of 27 different types of radiopharmaceuticals were tested on samples obtained through normal commercial channels. Failure to meet full specifications was observed in 10 of the 111 batches. All technetium-99m cold kits were reconstituted according to the directions in the package insert using sodium pertechnetate ( 99mTc) injection. Radionuclidic purity has been determined at the calibration time, except for Thallous [201Tl] Chloride injection where the highest impurity level up to product expiry is quoted. Non-compliance of the vial label was observed in one of the ten batches failing specification and was the sole cause of product failure for this batch. Vial label non-compliance consisted of, absence of volume in the vial. Six batches failed the biodistribution test but in no case did this involve failure of the distribution for the target organs. tabs

  7. Study of a new radiometric sterility test in radiopharmaceuticals

    A new radiometric method is studied for the determination of sterility. It is based on a culture marked with carbon-14 and the measurement by liquid scintillation of the radioactivity of the gaseous products released after a short period of incubation. The studied samples consisted in nonradioactive solutions and different radiopharmaceuticals, through a regulated current of nitrogen there is a transportation of gaseous and volatile products produced in each flask, which were received in a liquid scintillation vial. The experimental data permit to conclude that through the radiometric method the results can be obtained after 24 hours or less of incubation, instead of a period of several days which was necessary with the traditional process. Due to the sensitivity of the method it is possible to inoculate a minimum volume of sample, this is important in the case of the preparation of little parts for injection as it occurs generally with the pharmaceuticals. (author)

  8. Radiation protection optimization in practices for radiopharmaceuticals production at IEN

    This works has arisen from the need of updating radiological protection procedures, creating new ones and training qualified personnel to perform radiological protection duties in a nuclear facility. The main purpose of the research was to assess and minimize gamma and neutron dose rates emitted during the production and handling of radiopharmaceuticals at IEN/DIRA. A mobile measurements system (SMMG-N) was developed for on-site measurements. This system has proven to be more handy than the equipment formerly used for for this task. It has also proven to reduce the measurements uncertainties and to allow for the standardization of assessment procedures. He dose rates calculated using the data provided by this system have been compared with results obtained otherwise and good agreement was observed between them. This study has confirmed the need to improve the radiation shielding of KIPROS target-chamber and target vault in order to meet the radiological principles of dose rate limitation and optimization. (author)

  9. Aptamer-based therapeutics and their potential in radiopharmaceutical design

    Ferreira, Catia S.M. [The Open University Milton Keynes, (UNited Kingdom). Chemistry Dept.; University of Toronto, Ontario (Canada). Ontario Cancer Institute; E-mail: s.missailidis@open.ac.uk; Missailidis, Sotiris [University of Toronto, Ontario (Canada). Ontario Cancer Institute

    2007-09-15

    Aptamers, short, single stranded oligonucleotide entities, have been developed in the past 15 years against a plethora of targets and for a variety of applications. These range from inhibition of receptors and enzymes to the identification of small molecules in sensor applications, and from the development of targeted therapeutic to the design of novel diagnostic and imaging agents. Furthermore, aptamers have been designed for targets that cover a wide range of diseases, from HIV to tropical diseases, cancer and inflammation. Their easy development and flexibility of use and manipulation, offers further potential. In this paper we review their selection and consider some of the recent applications of aptamers in the design of radiopharmaceuticals for the targeted radiotherapy and medical imaging of disease. (author)

  10. Re-186-bleomycine: Radiopharmaceutic for diagnosis and therapy

    Bleomycine is an antibiotic used for chemotherapy of several neoplasms. Earlier studies with labelling of bleomycine (BLM) with different radionuclide were done. It was tested for different kind of tumours imaging. Due to previous encouraging imaging results with BLM-Tc-99m , BLM-Co-57 and BLM-In-111 authors decided to check the possibility and methods of labelling BLM with Re-186 to obtain radiopharmaceuticals potentially suitable for diagnosis and treatment of some neoplastic tumours. Different methods of labelling were investigated. The best one are electrolytic and with use of cationic-Sn complex modified by using of gentisic acid and incubation of the reaction mixture at 100 deg. C for 10 min. (author)

  11. Genetically significant dose from use of radiopharmaceuticals in Kuwait

    Since Kuwait, with 0.85 million inhabitants in 1973, has had a single nuclear medical service situated in one clinic for the past 10 yr it is possible to carry out a statistical evaluation of the radiation dose received by a defined population. The data collected from patients for the genetically significant dose (GSD) calculations are listed and the equation used in the calculations is given. The annual number of radionuclide procedures by age and sex in Kuwait in 1973, the annual GSD (microrad) due to application of radiopharmaceuticals in Kuwait in 1973 and a comparison of annual GSDs in various countries, are shown in tabular form. The results are discussed and in particular the high GSD in Kuwait, 52%, is attributed in part to therapy doses of 131I used for treatment of thyrotoxicosis which is relatively frequent in the country. (U.K.)

  12. Assay Validation For Quantitation of Sn 2+ In Radiopharmaceutical Kits

    An assay validation for quantitation of Sn2+ in radiopharmaceutical kits based on indirect iodometric titration is described. The method is based on the oxidation of sn2+ using a known excess of iodine and the excess unreacted iodine titrated with thiosulphate. Typical analytical parameters considered in this assay validation are precision, accuracy, selectivity or specificity, range, and linearity. The precision of the analytical method is quit good represented by coefficient of variance in range of 1.0% to 6.9 %, for 10 runs of analysis except one analysis shows the coefficient of 10.2 %. The method has an accuracy of 95.6 % - 99 % as percent recoveries at theoretical Sn2+ amounts of 463 μg to 2318μg

  13. Determination of stannous tin in radiopharmaceutical cold kits

    Two methods for determining stannous tin in 'cold kits', used for the preparation of Tc-99m labelled radiopharmaceuticals, have been developed. Both are based on the direct titration of the Sn2 in solution. In the first method titration is with N-bromosuccinimide. Of the materials commonly used as cold kits only albumin has been found to interfere with the determination. The second method is a standard iodometric titration in which starch is used as indicator. None of the materials tested interfere with this procedure. The N-bromosuccinimide method is the method of choice as the re-agent, a solid, can be used without prior standardization. Iodine solution must be standardized daily. The paper describes in detail the methods used and gives examples of kits in which the Sn2 levels have been determined using the described procedures

  14. FDA quality assurance for radioactivity in foods and radiopharmaceuticals

    The Food and Drug Administration (FDA) has regulatory responsibility for radionuclides in foods and radiopharmaceuticals and must maintain an ongoing Quality Assurance Program. These Quality Control Programs involve the U.S. Environmental Protection Agency (EPA) and the National Institute of Standards and Technology (NIST), who supply the necessary reference materials and standards to ensure that the measurements are accurate and reproduceable. Data from EPA (1987 to 1991) and from a NIST 'Blind' Source study (1985 to 1991) show the results are accurate with an average variation from NIST values of 1.8%. The use of standard materials with the same matrices as the samples being analyzed provides credibility to the measurements. (orig.)

  15. Preparation and evaluation of third generation technetium-99m radiopharmaceuticals

    The preparation and evaluation of three different 99mTc labelled peptides as third generation radiopharmaceuticals is presented. Lys3-Bombesin ([Lys3]BN), ubiquicidin 29-41(UBI 29-41) and Tyr3-octreotide (TOC) were prepared as instant kit formulations to be labelled by direct or indirect methods with 99mTc in order to evaluate in vivo prostate malignancies, infection processes and lung cancer respectively. Radiochemical purity of >93% was obtained. Also, high in vitro and in vivo stabilities and preservation of the molecular recognition were observed. It is demonstrated that 99mTc-EDDA/ HYNIC-[Lys3]BN detects GRP receptor positive tumours in mice, 99mTc-UBI 29-41 detects infection foci in humans and 99mTc-EDDA/HYNIC-TOC is useful in patients with lung cancer. (author)

  16. Solid support for [11C]cyanide labelling of radiopharmaceuticals

    [11C]HCN plays a major role in synthesis of 11C-labelled organic radiopharmaceuticals because of its on-line availability as a primary precursor of Carbon-11. [11C]HCN is usually trapped in 0.5-1.0 ml of 0.1 M NaOH or KOH solution for the synthesis of organic labelled compounds. Though [11C]HCN in 0.1 M base can be utilized for labelling base resistant organic compounds, substrates with esters, amide like functional groups cannot be labelled using this method due to the instability of these groups in basic medium. The authors report a novel approach for trapping no-carrier-added [11C]HCN on a silica gel support and its incorporation into model compounds

  17. Design of GMP compliance radiopharmaceutical production facility in MINT

    Full text: In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines, which provides radiation safety to the operator and the surrounding environment from radioactive contamination. In 1999, BPFK (Malaysia National Pharmaceutical Control Bureau) enforced the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. Among others, the guidelines require the pharmaceutical production facility to be designed based on cleanroom environment. In order to meet this requirement, the design of a radiopharmaceutical production facility shall combine the concept of radiation safety and cleanroom to ensure that both requirements from GMP and IAEA are met. This design requirement is necessary to ensure a radiopharmaceutical production facility which is safe, has high production quality and in compliance with the Malaysian and International standards. In order to obtain the license to continue producing radiopharmaceutical products, MINT shall closely follow the guidelines from PICS: GMP and nuclear facility requirements. To meet those requirements, the layout of MINT facility was redesigned to ensure the contaminants or particulates from outside area will not enter the production area. The flow path of personnel to the production room is equiped with air lock and change room in order to avoid contamination from outside environment. The airlock and changing room provide the physical separation of different stages of cleanroom class and between clean area and non-clean area. The cleanliness level or class for each room is determined by the criticality of exposure of the process and products to the environment. The clean class which is grade A is used for critical process and the other grade is for non-critical process or as a background. The concepts of

  18. Measurement of the activity of the radiopharmaceuticals used in therapy

    Sahagia, M.; Razdolescu, A.C.; Grigorescu, E.L.; Luca, A.; Ivan, C. [National Institute of R and D for Physics and Nuclear Engineering ' Horia Hulubei' IFIN-HH, POB MG-6, Bucharest (Romania)

    2006-07-01

    The paper presents the results obtained in the assurance of the whole traceability chain in the measurement of the activity for a particular group of radionuclides used as therapeutic pharmaceuticals: strong beta - weak gamma emitters, such as: 153 Sm, 177 Lu, 186 Re, 188 Re. The regulations regarding the uncertainty of the activity of therapy radiopharmaceuticals impose a maximum limit of 5%. All the above mentioned radionuclides belong to the group of triangular decay scheme and consequently they were standardized absolutely by the 4{pi}{beta}-{gamma} coincidence method. The solutions were then used for the calibration of the secondary standard, consisting from a 'Centronic I.G.12/20 A' ionization chamber. The calibration was transferred to the commercial radioisotope calibrators, as initial calibration figures. Some of these results are presented in the paper. (author)

  19. Triazacyclononane Phosphinic Acids (TRAP) as ligands for 68Ga radiopharmaceuticals

    Gallium-68 radiopharmaceuticals are the most interesting alternatives to those based on 18-F. 68-Ga is produced in commercial 68-Ge/68-Ga generator for fraction of the 18-F price. As metal isotope, 68-Ga must be tightly complexed by a suitable ligand. Macrocyclic ligands are the most suitable ones as their Ga3+ complexes are thermodynamically stable and kinetically inert. Till now, 68-Ga radiopharmaceuticals have been based on DOTA and NOTA skeletons but these ligands exhibit non-optimal labelling properties (high excess of the ligand, long heating, narrow pH range etc.). 1,4,9-TRiAzacyclononane Phosphinic acids (TRAP ligands) have been suggested as ligands for the fast and efficient 68-Ga incorporation. Due to low basicity of the phosphinic acid moieties as well as the ring nitrogen atoms, full complexation is possible even in highly acidic solutions (down to pH 1, i.e. pH of the neat generator eluate). Presence of weakly complexing atoms outside the ligand cage (oxygen atoms e.g. in TRAP-Pr or TRAP-OH) facilitates metal isotope incorporation in highly diluted solutions (non-carrier-added conditions) due to increasing effective metal ion concentration close to the macrocyclic cage. As very low excess of the ligands/conjugates is necessary for complexation, very high specific activity can be obtained. Unusual out-of-cage complexes were observed in the Ga-TRAP-OH system where deprotonated P-CH2O- groups participate in the Ga3+ coordination. The efficiency of 68-Ga labelling is also govern by selectivity of the TRAP ligands for Ga3+ over the most common impurities, e.g. Zn2+ and Fe3+ ions. The article is illustrated by the molecular schemes of NOTA, DOTA, TRAP-Pr and TRAP-OH

  20. The regional service for the preparation and distribution of radiopharmaceuticals in the west of Scotland

    The centralised preparation of radiopharmaceuticals was begun in 1965 for reasons of radiological safety and cost effectiveness. It enabled the provision of a single specially designed facility to process large quantities of radioactivity safely and avoided the distributed handling of radioactivity. Effective supervision of the safe usage and disposal of radionuclides in hospitals throughout the region became practicable. It also enabled the bulk purchase of radiopharmaceuticals with lower unit costs and their efficient utilisation due to the large number of users. Since 1965, great changes have taken place in the nature of the common radiopharmaceuticals. Most now have short physical half-lives and must be prepared close to their place of use. This has meant improving the pharmaceutical standards of the facilities and working methods. However, the reasons stated above for a centralised service are still applicable and have been reinforced by others arising from the need for good pharmaceutical manufacturing practice in current radiopharmaceutical production

  1. The use of a simple Karl Fischer apparatus for water determination in lyophilised radiopharmaceutical kits

    Small amounts of water have been determined in lyophilised radiopharmaceutical kits using a simple Karl Fischer Apparatus. The method can be applied to the determination of water in starting materials. The water present in zinc acetate dihydrate was determined. (author)

  2. Groningen experience in production and application of fluorine-18 and carbon-11 labeled radiopharmaceuticals

    In this presentation the preparation of these tracers (fluorine-18 and carbon-11 labeled radiopharmaceuticals), as well as the present stage of development and evaluation, and the potential application in oncology will be discussed. (author)

  3. VII. Boettstein Colloquium: PET-Radiopharmaceuticals at PSI: achievement and future prospects

    Schubiger, P.A.; Beer, H.F.; Blaeuenstein, P.; Leenders, K.E.

    1993-12-31

    The three sessions of the 1993 Boettstein colloquium dealt with the following topics: - PET-radiopharmaceuticals, - PET-scanning: significance of tracer uptake, - clinical options using PET. 22 papers were presented. figs., refs.

  4. VII. Boettstein Colloquium: PET-Radiopharmaceuticals at PSI: achievement and future prospects

    The three sessions of the 1993 Boettstein colloquium dealt with the following topics: - PET-radiopharmaceuticals, - PET-scanning: significance of tracer uptake, - clinical options using PET. 22 papers were presented. figs., refs

  5. International seminar on therapeutic applications of radiopharmaceuticals. Programme. Book of extended synopses

    The document includes extended synopses of 64 presentations given at the International Seminar on Therapeutic Applications of Radiopharmaceuticals, held in Hyderabad, India, 18-22 January 1999. A separate indexing was prepared for each presentation

  6. Research and production of radiopharmaceuticals in the CSSR and their future prospects

    The history is briefly outlined of the preparation of radiopharmaceuticals in Czechoslovakia and their current position in the Czechoslovak Pharmacopoeia. The radionuclides used most frequently in clinical practice in the CSSR include 131I, 99mTc and 113mIn. The overall consumption of radiopharmaceuticals in 1985 amounted to a value of over 25.5 mill. Czechoslovak crowns of which radiopharmaceuticals worth over 12 million crowns were manufactured in the country. It is pointed out that work with biological materials and autologous blood derivatives requires high hygiene standards. Thus, with the 4th edition of the Czechoslovak Pharmacopoeia to be put into force, the principles will also be enforced of the Good Manufacturing Practice in the preparation of radiopharmaceuticals in Czechoslovakia. (L.O.). 1 tab., 10 refs

  7. Quantitative studies in radiopharmaceutical science: Progress report, September 1, 1986 through August 31, 1987

    The reports in the study were processed separately for the data bases. Research involved attempts to improve PET imaging and diagnostic techniques in man. The primary radiopharmaceutical used was a form of fluorodeoxyglucose

  8. Development, preparation and control of sup(99m)Tc or sup(113m)In labelled stannous hydroxide radiopharmaceuticals. Part of a coordinated programme on radiopharmaceuticals

    The preparation of different sup(99m)Tc and sup(113m)In radiopharmaceuticals using stannous chloride was investigated. Chemical and radiochemical procedures for the quality control of these preparations were studied. Toxicity and biological controls of the preparation were carried out. Procedures for the preparation and control of the following radiopharmaceuticals have been standardized by the authors; albumin macroaggregates labelled with sup(99m)Tc, sup(113m)In and other isotopes for lung scanning; albumin microspheres labelled with sup(99m)Tc for lung scanning; sup(99m)Tc or sup(113m)In-labelled stannous hydroxide colloid for liver scanning; sup(99m)Tc-stannous phytate for liver scanning; sup(99m)Tc-Sn-dextrose, a new radiopharmaceutical which has been proposed by the authors and is now used in Mexico for renal and cerebral scanning and sup(99m)Tc-Sn pyrophosphate and diphosphonate for bone scanning

  9. Approaches to the design of clean air handling facilities for radiopharmaceuticals

    Manufacturing, handling and administering processes of radiopharmaceuticals have to meet the requirements of both the fields viz. ''radio'' activity and ''pharma'' activity. Both these fields often dictate conflicting requirements. A step by step analysis of these conflicts can lead to practices reasonably acceptable to both the fields. The design approaches include engineering concepts of radiation protection, concepts and practices for pharmaceuticals, biologically unsafe products/processes and manufacturing, handling and administering processes of radiopharmaceuticals

  10. Comparison of two methods of radiopharmaceuticals production and evaluation of their quality

    Two methods for the following five radiopharmaceuticals production were compared: sulfur colloid, diethylenetriamine pentaacetic calcium salt, phyrophosphate sodium, albumin aggregated, glucoheptonate calcium salt. Radiochemical purity was determined by electrophoresis, thin-layer chromatography and bio-distribution test in mice and rats. It was concluded that chromatographic method shows better efficiency and that bio-distribution test should be done only when testing new radiopharmaceuticals because the good correlation of this test with thin-layer chromatography. (author)

  11. Recent trends in the concept of specific activity: Impact on radiochemical and radiopharmaceutical producers

    In the radiochemical and radiopharmaceutical industry, the concepts and subsequent specification used for determining the purity of the radiopharmaceutical product are of concern to both the regulator and the producer. It is therefore of profound importance that these concepts such as specific radioactivity are used correctly and their meaning fully understood. Recent changes in the pharmacopoeias are evaluated and the implications thereof discussed. On the basis thereof suggestions are made for definitions, specifications and tests

  12. Metabolic radiopharmaceutical therapy in nuclear medicine; Terapia metabolica mediante radiofarmacos en medicina nuclear

    Reguera, L.; Lozano, M. L.; Alonso, J. C.

    2016-08-01

    In 1986 the National Board of Medical Specialties defined the specialty of nuclear medicine as a medical specialty that uses radioisotopes for prevention, diagnosis, therapy and medical research. Nowadays, treatment with radiopharmaceuticals has reached a major importance within of nuclear medicine. The ability to treat tumors with radiopharmaceutical, Radiation selective therapy has become a first line alternative. In this paper, the current situation of the different therapies that are sued in nuclear medicine, is reviewed. (Author)

  13. Trends in Radiopharmaceuticals (ISTR-2005). Proceedings of an International Symposium. Vol. 2

    The growth of nuclear medicine depends on advances in radiopharmaceutical development and discovery, as well as improvements in instrumentation. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the contributions of scientists from diverse disciplines such as chemistry, physiology and pharmacology. The IAEA has been supporting activities in the field of radiopharmaceuticals, which has resulted in significant capacity building in the above fields in Member States. Many Member States have developed manufacturing facilities through technical cooperation projects for the large scale production of radiopharmaceuticals which helped the growth of nuclear medicine in those countries. IAEA efforts through coordinated research projects have also helped in advancing research activities in the development and utilization of new products in many Member States. The International Symposium on Trends in Radiopharmaceuticals (ISTR-2005) was organized in order to provide scientists and professionals from 70 countries working in the field of radiopharmaceuticals and related sciences with the opportunity to present their research to an international audience. Sessions covered the most relevant topics of radiopharmaceuticals chemistry, including radionuclide production, radiochemical processing, manufacturing and quality control, quality assurance, latest advances in radiopharmaceuticals research, good manufacturing practices and regulatory aspects. On the basis of the invited presentations, papers and panel discussions during ISTR-2005, several areas of possible future international cooperation were identified. This publication comprises two volumes and constitutes a record of the symposium and includes a summary as well as invited papers presented. A CD-ROM containing the unedited contributed papers which were presented in the two poster sessions of the symposium is included in volume 2

  14. Trends in radiopharmaceuticals (ISTR-2005). Proceedings of an international symposium. Vol. 1

    The growth of nuclear medicine depends on advances in radiopharmaceutical development and discovery, as well as improvements in instrumentation. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the contributions of scientists from diverse disciplines such as chemistry, physiology and pharmacology. The IAEA has been supporting activities in the field of radiopharmaceuticals, which has resulted in significant capacity building in the above fields in Member States. Many Member States have developed manufacturing facilities through technical cooperation projects for the large scale production of radiopharmaceuticals which helped the growth of nuclear medicine in those countries. IAEA efforts through coordinated research projects have also helped in advancing research activities in the development and utilization of new products in many Member States. The International Symposium on Trends in Radiopharmaceuticals (ISTR-2005) was organized in order to provide scientists and professionals from 70 countries working in the field of radiopharmaceuticals and related sciences with the opportunity to present their research to an international audience. Sessions covered the most relevant topics of radiopharmaceuticals chemistry, including radionuclide production, radiochemical processing, manufacturing and quality control, quality assurance, latest advances in radiopharmaceuticals research, good manufacturing practices and regulatory aspects. On the basis of the invited presentations, papers and panel discussions during ISTR-2005, several areas of possible future international cooperation were identified. This publication comprises two volumes and constitutes a record of the symposium and includes a summary as well as invited papers presented. A CD-ROM containing the unedited contributed papers which were presented in the two poster sessions of the symposium is included in volume 2

  15. The anesthetics influence (ethilic-eter and urethane) on renal radiopharmaceuticals

    A comparative study was done using anesthetics like ether ethilic and urethane, in rats (Wistar). A significative variation was observed in the results obtained when renal radiopharmaceuticals were investigated. Using urethane, the renal uptake increase progressivelly due to the inhibition of the renal filtration and it starts to recuperate when the anesthetic effect was eliminated. Using ether ethilic the radiopharmaceuticals are quickly eliminated from the kidneys (tubular or glomerular filtration), showing that the renal function was protected. (author)

  16. Background information on the evaluation of radio-pharmaceuticals for marketing in Australia

    The article outlines how drug applications in Australia are processed by the various health authorities. The Therapeutic Goods Act regulates the magority of materials coming into Australia for human therapeutic use. Persons wishing to import radiopharmaceuticals must prepare on application to the Health Department. The data needed for these submissions is given in the article. The Australian Drug Evaluation Committee has the power to recommend materials for release. The current status of radiopharmaceuticals in Australia is also given

  17. Calibration and qualification of equipment in the pharmaceutical industry: emphasis on radiopharmaceuticals production

    The calibration and qualification of equipment are listed items in RDC number 17 of 2010 which refers about the Good Manufacturing Practice (GMP) of medicaments and RDC number 63 of 2009 which refers about GMP of Radiopharmaceuticals. Both are essential requirements since they are involved in process control to attend the regulatory criteria and are a key part of the validation process. The aim of this work is presenting the importance of calibration and qualification, and the routine use of equipment and facilities in industrial scale production of radiopharmaceuticals in the IPEN/CNEN. The radiopharmacy of IPEN is a pharmaceutical industry that produces radiopharmaceuticals for diagnosis and therapy. It was the pioneer institute in production of radioisotopes and radiopharmaceuticals in Brazil. Currently, 38 products are distributed to the nuclear medicine centers, including primary radioisotopes, labeled molecules and lyophilized reagents for labeling with technetium-99m. To fulfill the GMP requirements for quality assurance of products, several factors must be considered including infrastructure, equipment and raw materials beyond, obviously, the whole production process should be controlled until the release of the final product. Therefore, the calibration and verification of equipment, instruments and other appliances used in the production and quality control should be performed. A program of calibration, qualification and requalification of equipment used in production and quality control of radiopharmaceuticals is necessary for the validation of production processes and analytical methods, and should be established for quality assurance of produced radiopharmaceuticals. (author)

  18. Calibration and qualification of equipment in the pharmaceutical industry: emphasis on radiopharmaceuticals production

    Melero, Laura T.U.H.; Silva, Katia S. da S.; Zanette, Camila; Araujo, Elaine B. de; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The calibration and qualification of equipment are listed items in RDC number 17 of 2010 which refers about the Good Manufacturing Practice (GMP) of medicaments and RDC number 63 of 2009 which refers about GMP of Radiopharmaceuticals. Both are essential requirements since they are involved in process control to attend the regulatory criteria and are a key part of the validation process. The aim of this work is presenting the importance of calibration and qualification, and the routine use of equipment and facilities in industrial scale production of radiopharmaceuticals in the IPEN/CNEN. The radiopharmacy of IPEN is a pharmaceutical industry that produces radiopharmaceuticals for diagnosis and therapy. It was the pioneer institute in production of radioisotopes and radiopharmaceuticals in Brazil. Currently, 38 products are distributed to the nuclear medicine centers, including primary radioisotopes, labeled molecules and lyophilized reagents for labeling with technetium-99m. To fulfill the GMP requirements for quality assurance of products, several factors must be considered including infrastructure, equipment and raw materials beyond, obviously, the whole production process should be controlled until the release of the final product. Therefore, the calibration and verification of equipment, instruments and other appliances used in the production and quality control should be performed. A program of calibration, qualification and requalification of equipment used in production and quality control of radiopharmaceuticals is necessary for the validation of production processes and analytical methods, and should be established for quality assurance of produced radiopharmaceuticals. (author)

  19. Legal aspects of the production and application of radiopharmaceuticals in Germany

    This article deals with the regulation of the production and use of radiopharmaceuticals in Germany. As in other countries, radiopharmaceuticals may be used when licensed by the German equivalent of the Federal Drug Agency or in clinical trials. Furthermore, non-licensed radiopharmaceuticals can be administered to patients for diagnosis when they are produced in the same institution and not more than 20 doses per week and radiopharmaceutical are given. A prerequisite for these three ways of use is the production of the radiopharmaceutical in question according to the guidelines of the good manufacturing practice (GMP) which creates considerable problems for the usually small PET centers installed in the German university hospitals. German law offers a further possibility to apply non-licensed radiopharmaceuticals for clinical purposes: their administration to patients is not forbidden when performed by a physician who produces the substance himself or is at least responsible for its synthesis. This regulation has, however, been met with criticism by government agencies. (orig.)

  20. HPLC-MS technique for radiopharmaceuticals research and control

    A liquid chromatography/refractive index detector/radiometric detector/ mass spectrometric detector combination (Agilent 1100 HPLC/RAD/DAD/RID/MSD system) is used as a complex technique for quality assessment of radiopharmaceuticals such as 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Optimisation of HPLC/MS analysis was performed investigating the electrospray ionisation (ESI) analytical signal of the mass spectrometer as a function of solvent composition. The anion-exchange eluents applied as specified by the pharmacopoeia are not suitable for ESI detection due to high ion concentrations. Therefore, solutions of glucose in methanol/water and acetonitrile/water solutions of various semi-volatile electrolytes (ammonium chloride, formic acid, ammonium formate) were analysed by flow injection analysis (FIA) and chromatographically. The best analytical response was obtained with acetonitrile : 0.25% ammonium formate = 80:20 solutions. The most intense MSD signals of FDG in ammonium formate were obtained for the following complex ions: (i) positive ions: fdg.NH4+, fdg.Na+ and (fdg2-CH3O).Na+ (m/z = 200, 205 and 344); (ii) negative ions: fdg.Cl- and fdg.HCOO- (m/z= 217 and 227). The HPLC-MS analysis with Zorbax C-18 and Asahipak-NH2P50 columns gave evidence of admixtures and radiolytic formation of deoxyglucose, deoxychloro-glucose, erythrose, erythritol, gluconic acid, lactose, raffinose, saccharic acid, sorbitol/[19F]FDG, sorbitol/[19F]FDG, xylitol, and other compounds. However, radiometric analysis of expired samples of [18F]FDG gave evidence of a very high radiation stability of its water-ethanol solutions at the point of output of radioactive products. Remarkable is the exceedingly high complexity of the mass spectra of FDG as compared to glucose. Therefore, further research concerns the influence of sodium chloride, linearity of signal response, impurities (mannitol, mannose etc.) interference, and robustness of the MS analysis, with special attention to the ratio of

  1. Therapeutic applications of radiopharmaceuticals. Proceedings of an international seminar

    The potential of radionuclides in therapy has been recognised for many decades. A number of radionuclides such as iodine-131, phosphorous-32, yttrium-90 and 1-131 MIBG have been in use for the treatment of many benign and malignant disorders. Recently, however, there has been a significant growth of this branch of nuclear medicine with the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain, neuroendocrine and other tumours. The prospect of localising or treating neoplastic diseases using specific antibodies labelled with radioactive isotopes capable of delivering large amounts of internally administered radiation may have the potential to fulfil the promise of EhrIich's 'magic bullet', which has tantalised investigators worldwide for the past sixty years. Recent success in this area has been largely due to genetic and molecular techniques that now permit production of a large number of suitable peptides and monoclonal antibodies directed against specific epitopes individually characteristic of specific tumours. The input of the radiochemist and the development of labelling techniques that do not destroy the immunological integrity of the monoclonal antibodies have also been essential ingredients of the success story. Recent significant advances in monoclonal antibody techniques for pretargeting make it very likely that radiopharmaceuticals will become an important part of therapy for various cancers. It may also be possible that in addition to the use of beta particles, alpha particles may soon become a mainstay of therapeutic nuclear medicine. Cancer researchers, looking for an extremely potent and highly specific way to target cancer cells, are investigating the use of monoclonal antibodies and peptides attached to alpha emitting radionuclides in early clinical trials. Today the field of radionuclide therapy is going through an extremely interesting and exciting phase and is poised for greater growth

  2. Activities, procedures and doses in pediatric patients due to radiopharmaceuticals

    Silvia Maria Velasques de Oliveira

    2008-12-01

    Full Text Available An investigation performed between 2003 and 2005 in sixteen selected public and private institutions in Northeast, Southeast and South geographical regions of Brazil evaluated average organ doses and effective doses in 2,411 pediatric patients due to diagnostic procedures with radiopharmaceuticals. For 1 year, effective doses were greater than literature. For 5 years, differences were noticed between present work and literature for bone scintigraphy, thyroid scintigraphy and 67Ga citrate scintigraphy. These differences may be attributed to the uncertainties in internal dose calculations. High absorved doses in bone surfaces of children due to 67Ga citrate and bone scintigraphy should be evaluated accordingly. Current protocols used recommend standardized mean activities per mean weight for all ages. However, it was observed that the activities were not standardized and were higher for children with younger ages. Future studies are needed for optimising activities of radiopharmaceuticals to these patients in the country.Foi realizado no Brasil, no período 2003-2005, um estudo sobre doses absorvidas em órgãos e doses efetivas devido ao uso de radiofármacos em pacientes pediátricos. Foram estudadas 2.411 crianças e adolescentes menores de 18 anos. Foi observado que as atividades usadas não foram padronizadas, sendo maiores para crianças de menor idade, podendo ser otimizadas conforme apropriado. Para 1 ano, as doses efetivas foram maiores do que as publicadas na literatura e para 5 anos, foram observadas diferenças para cintilografias ósseas, cintilografias da tireóide, e pesquisas de corpo inteiro com citrato de 67G. Deve ser avaliado se doses absorvidas em órgãos, especialmente para superfície óssea devido a cintilografias ósseas com 99mTc MDP e pesquisa de corpo inteiro com citrato de 67Ga podem acarretar risco radiológico adicional aos pacientes, considerando-se as peculiaridades de seu estado clínico.

  3. Radiopharmaceuticals for diagnosis of inflammation; Radiopharmaka fuer die Entzuendungsdiagnostik

    Meller, B.; Baehre, M. [Luebeck Univ. (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2007-06-15

    Inflammations represent mediator-induced reactions of the hematopoetic-immunologic cell system resulting from exogenous or endogenous stimuli. On cellular level, an increased expression of inflammatory genes is followed by the release of several mediators. As inflammatory response vascular permeability increases and interstitial oedema develops. Additionally, white blood cells emigrate and several transduction cascades are activated. Radiopharmaceuticals for inflammation scintigraphy should specifically reflect one or several aspects of inflammation pathophysiology on molecular level. A group of elder tracers for this purpose comprised substances that are accumulated due to the permeability of physiological barriers. However, their property to accumulate in all processes with increased vascular permeability results in a comparably low specificity of these methods. In-vitro-labelled granulocytes were the method of choice for scintigraphic imaging of inflammation for years. Investigations with {sup 111}In-labelled granulocytes are still frequently considered as the gold standard to detect inflammation by scintigraphy. The use of antibodies or antibody fragments directed against leucocytes allowed in vivo labelling and substituted more complex techniques of in vitro labelling despite of several disadvantages. Due to the superior imaging quality of positron emission tomography, [{sup 18}F]FDG-labelled leucocytes might result in a renaissance of in vitro methods. In cases of cerebral inflammation, activated microglia was visualised by its increased expression of benzodiazepin receptors. An interesting approach to differentiate between infection and sterile inflammation could be the use of bacterial gyrase inhibitors labelled with radioactive compounds. At present, specificity of this method is still controversially discussed. In search of substances to visualise inflammatory transduction cascades selectively, several chemotactic and chemokinetic cytokines, metabolites

  4. Standard of Practice Specific to Positron Emission Tomography (PET) Radiopharmaceuticals in Saudi Arabia

    Radiopharmaceuticals are essential tools for understanding human physiology and biochemistry, and subsequently, for the diagnosis and therapy of an extensive variety of diseases. Of the various cyclotron produced radiopharmaceuticals, positron emission tomography (PET) radiopharmaceuticals are being increasingly utilized in nuclear medicine imaging for both research and routine clinical diagnosis. The non-invasive PET imaging modality is unique in its ability to measure functional and metabolic activities of the body organs or tissues. These images are not available with other imaging technologies, such as CT, MRI or X-ray. With the aim of providing quality clinical service for the patients, acquiring most up-to-date imaging modality, PET has advanced exceptionally in the developed countries and with limited prevalence in developing countries. This must be attributed to the cost and complexity of such practice, in addition to the requirement of cyclotron and a radiochemistry laboratory on site for radiopharmaceuticals production. Our vision is to make the Kingdom of Saudi Arabia self-sufficient in all its requirements of radiopharmaceutical products as well as supplying the neighboring countries with such products for a comprehensive diagnostic and therapeutic care of the population. The Cyclotron and Radiopharmaceuticals Department (C and R) at the King Faisal Specialist Hospital and Research Center is a unique combination of advanced accelerator technology, radiochemistry, radiopharmacy, and radiopharmaceuticals research. A diverse staff composed of engineers, chemists, pharmacists and scientists work jointly with an aim to develop and manufacture SPECT and PET radioisotopes and their radiopharmaceutical products for on-demand availability in the clinical care of patients. The C and R Department ensures that it manufactures PET radiopharmaceutical products according to the international guidelines of Good Manufacturing Practices (GMP) and Good Radiopharmacy

  5. State of the art and perspectives in radiopharmaceutical field since ACOMEN 8. International Conference (Bordeaux May 11-13, 2005)

    Since previous ACOMEN conference in 2005 on radiopharmaceuticals, many improvements have been encountered: active research has allowed the development of numerous new tracers of interest, with a large part dedicated for PET; clinical applications of radiopharmaceuticals have resulted in patients care improvement, both for management and survival; therapeutic applications are now fully recognized, as internal targeted radiotherapy could be considered as efficient in several cancer diseases; and regulation, despite remaining difficulties, will certainly become more favourable for radiopharmaceuticals. Thus we could make sure that radiopharmaceuticals use will be even more established in the next years. (authors)

  6. Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1984-December 31, 1984

    This report presents progress in the areas of cardiac nuclear medicine, other imaging studies, investigations with biomolecules, and assessment of risks associated with the clinical use of radiopharmaceuticals

  7. Report of the consultants meeting on good manufacturing practices and clean room requirements for radiopharmaceuticals

    Radiopharmaceuticals are compounds containing radioisotopes that are used in nuclear medicine for a variety of diagnostic studies and, to a limited extent, for therapy. Almost 80% of the diagnostic studies are carried out with 99mTc containing radiopharmaceuticals (half-life, six hours). Recently, another class of radiopharmaceuticals contains the ultra short-lived isotopes 11C, 13N and 15O as well as 18F, which are mostly produced and immediately used in the hospital cyclotron Positron Emission Tomography (PET) facilities. In therapy, 131I is widely used for thyroid disorders, 32P for treatment of abnormal increase in circulating red blood cells, while 153Sm and 89Sr are used for palliation of pain in patients suffering from bone metastases. They contain very small amounts of chemical ingredients, normally do not have any pharmacological effects, and are administered in small volumes. Radiopharmaceuticals are produced, used and exported both in developing and developed countries. The scale of production is small compared to conventional pharmaceuticals. Monographs on radiopharmaceuticals can be found in many pharmacopoeias, such as BP, USP, EP and other compendia. This field is also marked by active research and development of new products both for diagnosis and therapy. Traditionally, production and supply of radiopharmaceuticals started as research activities of national nuclear laboratories operating reactors and cyclotrons. Certain products found useful and effective were continued to be provided to the clinics as a service from the nuclear centres. In developed countries demand of radiopharmaceuticals is so considerable that production and sale are increasingly taken over by commercial companies. On the other hand, in many developing countries, demand is still limited, and radiopharmaceutical production and supply still remain more of a service operation at the national nuclear centres. Depending on the radioactivity levels handled, production has to be

  8. Drugs that alter biodistribution and kinetics of radiopharmaceuticals

    Target localization and organ biodistribution of radiopharmaceuticals (RPs) may be altered by non-radioactive drugs whose pharmacological mechanisms compete with the RPs for the same retention processes. Originally referred to as side effects or incompatibilities, such interactions became a major concern in evaluating Nuclear Medicine procedures, as they might cause interpretation of the latter to be without value or misleading. With accumulated experience, some interactions were intentionally included in Nuclear Medicine procedures and became an additional tool in differential diagnosis. Moreover, due to the ability of some RPs to compete with therapeutic agents, Nuclear Medicine studies shifted from anatomical-physiological to more pharmacologically-pathologically-based procedures that can also monitor the stage of disease, and follow its treatment. The aim of this review, therefore, is not only to illustrate some crucial pharmacological issues in Nuclear Medicine imaging, but to emphasize the possible input that alterations of RP biodistribution by drugs may have in achieving better and safer diagnosis, disease staging and monitoring of the patient's response to therapy. 166 references

  9. Some radiopharmaceuticals derived from carbon-eleven labelled phosgene

    This thesis deals with some applications of the short lived cyclotron produced radioisotope carbon-11 (half life 20.4 min.) For medical use. Both chemical manipulation of highly radioactive gamma emitting material in order to prepare suitable 11C-labelled radiopharmaceuticals and two clinical studies are discussed. The first chapter comprises a general introduction concerning the application of the ''tracer principle'' to the short lived positron emitting radionuclides 18F, 11C, 13N and 15O in medicine. Chapter two deals with the synthesis of 11COCl2. This product is a useful new 11C-synthon with many potential applications. In chapter three the synthesis of 11C-urea from 11C-phosgene for medical use is described. The method uses the reaction of 11COCl2 with aqueous ammonia. Chapter four deals with the synthesis of 11C-barbituric acids and 11C-hydantoins and presents a clinical study on epilepsy, using 2-11C-5,5-diphenylhydantoin (11C-DPH). Patients having intractable epilepsy and patients having no epilepsy were given intravenously a single dose of 11C-DPH after which the accumulation of the radioactivity in the brain was followed by positron emission tomography. No regional concentration differences could be found near epileptic foci. There was a faint indication that there are some differences in uptake for whole brain between the two categories of patients. (Auth.)

  10. Technetium-99m Radiopharmaceuticals for Monitoring Drug Resistance. Chapter 12

    Resistance to chemotherapy constitutes a major obstacle to cancer cures. Cellular mechanisms of resistance involve efflux pumps, P-glycoprotein (Pgp), the product of the MDR1 gene and the related membrane glycoprotein, multidrug resistance associated protein 1 (MRP1). Multidrug resistant cell lines overexpressing Pgp are resistant to a structurally and functionally diverse group of chemotherapeutic agents. Many of these drugs tend to be lipophilic and positively charged at neutral pH. This suggested the application of the two lipophilic cationic 99mTc radiopharmaceuticals currently used for myocardial perfusion, 99mTc-MIBI and 99mTc-Tetrofosmin. Efforts were also made to develop specific 99mTc labelled substrates for Pgp based on lipophilic cationic 99mTc complexes. A large number of studies indicated that 99mTc-MIBI, 99mTc-Tetrofosmin and some related 99mTc compounds are substrates for Pgp. However, it remains uncertain whether these 99mTc labelled compounds are substrates for MRP1. Thus, both 99mTc-MIBI and 99mTc-Tetrofosmin would be general probes of transporter mediated multidrug resistance in tumour cells. (author)

  11. Standardization of quality control of radiometals and radiopharmaceuticals

    Purity of radiopharmaceuticals is not based on the chemical purity, but mostly quantified by measuring radiochemical purity (RCP). Even the expressions of successful radionuclidic labelling and RCP of radio ligand, like radiolabelled peptides are a source of potential confusion. There are no criteria in the field of Nuclear Medicine to qualify HPLC-separation methods. Typically RCP of radioligands is measured by HPLC and expressed as % of radio detected peak area (e.g expressed in μV.sec-1) of the intact radioligand vs. all other radio peaks measured during the same HPLC-run. Whereas, differences in eluents, gradient, flow, column (type and length), detector (material and size), connecting tubing (material, diameter, etc), software will most likely result in detection of different degrees of (im)purity, and thus variation in RCP. Therefore, since RCP are actually expressed in % of Arbitrary Units and a statement on the required purity of minimal 95%, as mentioned above, is open for discussion. Moreover, there are other quality control parameters in our field, e.g. Radionuclidic purity with questionable dimensions. Proposals for standardization will be presented

  12. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation

  13. Evaluation of SPECT quantification of radiopharmaceutical distribution in canine myocardium

    This study evaluates the quantitative accuracy of SPECT for in vivo distributions of 99mTc radiopharmaceuticals using fanbeam (FB) and parallel-beam (PB) collimators and compares uniform and nouniform attenuation correction methods in terms of quantitative accuracy. SPECT quantification of canine myocardial radioactivity was performed followed by well counter measurements of extracted myocardial tissue samples. Transmission scans using a line source and an FB collimator were performed to generate nonuniform attenuation maps of the canine thorax. Emission scans with two energy windows were acquired. Images were reconstructed using a filtered backprojection algorithm, with a dual-window scatter subtraction combined with either no attenuation compensation or single iteration Chang attenuation compensation based on a uniform attenuation map μ=0.152 cm-1 or the nonuniform transmission map. The measured mean counts from the SPECT images were converted using the well counter. The experimental results demonstrate that, compared with well counter values, the in vivo distributions of 99mTc were most accurately determined in FB and PB SPECT reconstructions with nonuniform attenuation compensation, under-estimated without attenuation compensation and overestimated with uniform attenuation compensation. 37 refs., 9 figs., 10 tabs

  14. FDA's requirements for radiation dosimetry of radiopharmaceutical drug products

    The primary concern of the Office of Drug Research and Review of the Food and Drug Administration in the field of radiation dosimetry is to ensure that radiopharmaceutical drug products are safe when used as investigational drugs (INDs) and are both safe and effective when a new drug application (NDA) is approved. In order to accomplish this, the sponsor of either an IND or applicant in the case of NDA must provide information that clearly describes the radiation dose that a patient will receive from the administration of the drug. The submitted numerical estimates of the radiation dose should be based on an absorbed fraction method of radiation dose calculation, such as the system set forth by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine or the system set forth by the International Commission on Radiological Protection (ICRP). This presentation will describe in detail the data that a sponsor of an IND needs to submit to satisfy the regulatory requirements. Examples will be given of common mistakes and omissions by sponsors in their presentation of data

  15. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS.

    Alexoff, D.L.

    2001-09-21

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation.

  16. Radiopharmaceuticals for bone lesions. Imaging and therapy in clinical practice

    Pauwels, E. K. J.; Stokkel, M. P. M. [Leiden University Centre, Dept. of Radiology, Division of Nuclear Medicine, Leiden (Netherlands)

    2001-03-01

    Bone scintigraphy continues to be one of the most commonly performed procedures in nuclear medicine. The radionuclide bone scan remains an excellent modality to detect metastatic disease in patients suffering from primary malignancies. This article reviews a number of aspects of bone scintigraphy such as bone physiology, radiopharmaceuticals and uptake mechanisms. As {sup 99}mTc labelled bis(di)phosphonates are the most frequently used this article is centred around these imaging agents. In addition to diagnostic bone scintigraphy the use of various bone seeking agents has been extended to the palliative treatment of bone metastases. In this context the radiobiological characteristics of various radionuclides as {sup 89}Sr, {sup 32}P, {sup 153}Sm, {sup 186}Re and {sup 117}Sn is elucidated. In addition, the clinical efficacy for pain killing of these radionuclides is elucidated on the basis of the radiation properties of these agents. It is concluded that {sup 89}Sr and {sup 186}Re are presently the radionuclides of choice. The latter agent has a slight advantage as its imaging photons enable individual dosimetry, resulting in an optimised application scheme.

  17. Testing of radiopharmaceuticals by HPLC: continuation and end

    We presented last year a new testing technique of radiochemical purity by HPLC applicable in numerous radiopharmaceuticals. But, it was not efficient for usual tracers such as the HMDP or DTPA. We have developed a new method for these molecules. As materials we made use of: - the HPLC Waters system equipped with the code Millenium; - the U.V.Waters 486 detector set to 300 nm; - the Flow count-Bioscan (Wallac) radioactivity detector; - the column Waters Nova-pak, C18 60A 4μm, 3.9 x 150 mm. Concerning the method, we made use of gradient separation method as follows: for 0→3 min: 100% butanol-1, 0.7 ml/min; for 3→ 17 min: passage by 100% water by linear gradient; and for 7 → 15 min: gradual flow-rate augmentation to 2 ml/min. We obtained for the retention time (RT) of pertechnetate the value 2 min. This method allows separating the HMDP, the Phytate, the DTPA and the DMSA which present an identical RT of 10.5 min. The hydrolyzed and reduced Tc was not made evident. In conclusion, due to its facility, rapidity and low cost this methodology may be used on a routine base to test the radiochemical purity of these four tracers in a service equipped by a HPLC

  18. Investigation on chemistry of model compounds of technetium radiopharmaceuticals

    The report summarized experimental and theoretical results concerning the chemical structures and the biodistribution of hydrophilic technetium chelates with hydroxycarboxylic and aminopolycarboxylic acids, thiol compounds and aliphatic and aromatic nitrogen compounds as ligands. Methods which are suitable for synthesizing and characterizing defined chelates of Tc(V), Tc(IV) and Tc(III) have been developed for crystlline substances and species in solution, respectively. For certain types of technetium chelates three dimensional structure models were calculated from atomic parameters. The electron energies and electron distribution of Tc(V) thiol compounds were calculated by quantum chemical methods in order to interprete physical properties of these substances. Biodistribution studies revealed relationships between the osteotropic behaviour and the structure of phosphorous and non-phosphorous technetium chelates and between the kidney uptake and ligand exchange ability of Tc(V) hydroxycarboxylates. Important parameters for the production of technetium-99m kits have been elaborated and used for the optimization of radiopharmaceuticals (bone-, kidney and hepatobiliaer agents). (author)

  19. In Vitro Assessment of the In Vivo Stability of Cu-64 Radiopharmaceuticals

    Packard, Alan B

    2011-12-15

    Research Plans: The successful development of Cu-64 radiopharmaceuticals depends upon retention of the Cu-64 atom in the radiopharmaceutical. To date, the focus has been on the development of chelators that better retain Cu-64, but there has been no effort to develop an effective method by which improved retention may be measured. In the absence of a suitable analytical method, the stability of Cu-64 radiopharmaceuticals is estimated indirectly, with decreased liver uptake suggesting higher in vivo complex stability. But this approach is inadequate for radiopharmaceuticals, such as radiolabeled antibodies, that are expected to accumulate in the liver even when there is no free Cu-64 present. The absence of such a method has also hampered efforts to systematically evaluate the chemical factors that may give rise to improved retention. The objective of this project is to develop and validate such a method. Accomplishments: The two primary accomplishments of this project will be 1) the development and validation of a method to measure the stability of Cu-64 radiopharmaceuticals and 2) the determination of the chemical factors that define the in vivo stability of Cu 64 radiopharmaceuticals. Because Cu(II) is extremely labile, the in vivo stability of Cu-64 radiopharmaceuticals is not primarily determined by the amount of free Cu that is present at any given time or by the thermodynamic stability constants, but rather by the rate at which Cu is lost from the complex, the dissociation rate constant, kd. The dissociation rate constants of the Cu-64 complexes from a series of bifunctional chelators (BFCs) will be measured using Free Ion Selective Radiotracer Extraction (FISRE), a technique originally developed to measure bioavailable Cu in environmental samples. FISRE will also be applied to the determination of the kd's of a series of reference Cu-64 complexes to determine the chemical factors that define the in vivo stability of Cu-64 radiopharmaceuticals. Potential

  20. Querying Versioned Software Repositories

    Christopeit, Dietrich; Böhlen, Michael; Kanne, Carl-Christian; Mazeika, Arturas

    2011-01-01

    Large parts of today's data is stored in text documents that undergo a series of changes during their lifetime. For instance during the development of a software product the source code changes frequently. Currently, managing such data relies on version control systems (VCSs). Extracting information from large documents and their different versions is a manual and tedious process. We present {\\sc Qvestor}, a system that allows to declaratively query docume...

  1. Querying versioned software repositories

    Christopeit, Dietrich; Böhlen, Michael H.; Kanne, Carl-Christian; Mazeika, Arturas

    2011-01-01

    Large parts of today’s data is stored in text documents that undergo a series of changes during their lifetime. For instance during the development of a software product the source code changes frequently. Currently, managing such data relies on version control systems (VCSs). Extracting information from large documents and their different versions is a manual and tedious process. We present Qvestor, a system that allows to declaratively query documents. It leverages information about the str...

  2. Trends in indigenous radioisotope and radiopharmaceutical production in Bangladesh

    There are 17 nuclear medicine centres (NMC) in Bangladesh which are distributed all over the country. The objective of RIPD is to produce short lived radioisotopes and radiopharmaceuticals for these NMCs. Iodine-131 generated during irradiation of natural TeO2 in the 3 MW TRIGA research reactor is separated by dry distillation method. Recently two independent dry distillation apparatus were installed in the 131I production plant for alternate use at RIPD. Since July 2003 more than 11Ci of 131I solution has been produced. At present, on average, 300mCi of 131I is produced on a weekly basis by irradiating about 38.5g of TeO2 at 2.5 MW for 15 h of interrupted irradiation. Due to the limitation in reactor operation time and target size, RIPD meets only a part of country's demand for 131I. Increase of reactor operation time and installation of more dry central thimble (DCT) in the reactor to irradiate more than one target at a time is under active consideration of the authority. Equipment for diagnostic and therapeutic 131I capsule production has recently been installed at RIPD. Test production of diagnostic 131I capsules has been done successfully. Therapeutic capsule production will be started when 131I solution with required radioactive concentration will be available. RIPD started its activity with the production of instant 99mTc by solvent extraction method by irradiating natural molybdenum (as MoO3) target in 1987. In 1988 the Division produced 99mTc-sublimation generator by irradiating titanium molybdate in the reactor. A facility for the production of chromatographic 99mTc-generator was installed at RIPD under IAEA TC Project BGD/4/014 in 1997. In this facility four 99mTc-generators per batch can be produced. So far 100 batches of 15GBq 99mTc-generators have been produced from imported fission 99Mo. Yearly production of 99mTc-generatos is shown in Fig.1. Users comment regarding the quality and performance of the locally produced 99mTc-generator are quite

  3. Hepatic extraction fraction of hepatobiliary radiopharmaceuticals measured using spectral analysis.

    Murase, K; Tsuda, T; Mochizuki, T; Ikezoe, J

    1999-11-01

    Measuring the hepatic extraction fraction (HEF) of a hepatobiliary radiopharmaceutical helps to differentiate hepatocyte from biliary tract diseases, and it is generally performed using deconvolution analysis. In this study, we measured HEF using spectral analysis. With spectral analysis, HEF was calculated from (the sum of the spectral data obtained by spectral analysis--the highest frequency component of the spectrum) divided by (the sum of the spectral data) x 100 (%). We applied this method to dynamic liver scintigraphic data obtained from six healthy volunteers and from 46 patients with various liver diseases, using 99Tcm-N-pyridoxyl-5-methyltryptophan (PMT). We also measured HEF using deconvolution analysis, in which the modified Fourier transform technique was employed. The HEF values obtained by spectral analysis correlated closely with those obtained by deconvolution analysis (r = 0.925), suggesting our method is valid. The HEF values obtained by spectral analysis decreased as the severity of liver disease progressed. The values were 100.0 +/- 0.0%, 94.7 +/- 13.6%, 76.2 +/- 27.4%, 45.7 +/- 15.6%, 82.7 +/- 24.2% and 95.2 +/- 11.8% (mean +/- S.D.) for the normal controls (n = 6), mild liver cirrhosis (n = 16), moderate liver cirrhosis (n = 11), severe liver cirrhosis (n = 5), acute hepatitis (n = 8) and chronic hepatitis groups (n = 6), respectively. The HEF was obtained more simply and rapidly by spectral analysis than by deconvolution analysis. The results suggest that our method using spectral analysis can be used as an alternative to the conventional procedure using deconvolution analysis for measuring HEF. PMID:10572914

  4. Quality control of radiopharmaceutical dose calibrators in nuclear medicine unit

    As part of the program to ensure quality in nuclear medicine unit, in addition to diagnostic procedures, are evaluated activity meters, which is intended to measure the aliquot of radiation of radionuclides and / or radiopharmaceuticals that are administered to patients undergoing diagnostic investigation and / or therapeutic treatment. The good operating condition of dose calibrators is essential to ensure efficiency, safety and reliability of the measurements, once the lack of accuracy in the responses of these equipments can cause significant errors in the activity administered to the patient and may result in poor quality images resulting in the repetition of examis and interference in the successful treatment of the patient. This study aims to, considering the need for constant evaluation of the functioning of the activity meters and the fact that this issue be part the responsibilities of the professional of radiology, perform quality control testing of these instruments in relation to the most recent norm of National Commission of nuclear Energy (CNEN-NN 3:05) in Brazil, that is also in according to the international standards and reference values established during acceptance testing of these instruments in a nuclear medicine service. For this, was made a review of specific literature and the use of barium, cobalt and cesium to the tests in a nuclear medicine service of the state of Pernambuco in Brazil. The obtained results of the specific tests utilized to verify the correct working of the dose calibrators show coherency with the resolutions of the CNEN-NN 3:05 and are also in agreement with the international standards to that the measurement of activities be made with accurate results and thereby contribute to the proper functioning of nuclear medicine service. (authors)

  5. The 2. International Conference on Radiopharmaceutical Therapy (ICRT-2007)

    The 2nd ICRT was organized by the WRPTC in collaboration with the First State Central University Hospital of Ulaanbaatar, which has the only NM center in far-away Mongolia, serving as host. The meeting was also made possible through the joint collaborative efforts of several regional and international organizations like, ARCCNM, DOE-USA, EANM, AOFNMB, ANZSNM, Mongolian NMS and the Mongolian Radiological Society. This whole event from its very conceptualization, planning and implementation was made possible under the absolute and dynamic leadership of the Chairman of the WRPTC Prof. Ajit Padhy. A total of 210 participants coming from 67 countries attended the conference. The 5-day event was divided into 17 scientific sessions. A total number of 45 invited lectures and 218 proffered scientific papers (25 oral and 193 poster presentations) were presented. The topics covered in the conference included the current trends in almost all areas of radionuclide therapy including clinical applications, radiation protection, radiation dosimetry, medical physics, radiopharmacy and molecular therapy. Radionuclide treatment of thyroid disorders, metastatic bone pain, liver cancer, lymphoma, neuroendocrine tumours, rheumatoid arthritis, hemophilic haemarthropathy formed the main bulk of the scientific presentations. Several important scientific presentations which are of great importance for the practice of radionuclide therapy in the developing countries, were made using relatively new radiopharmaceuticals involving Lutetium 177, Tin-117m and Re-188. Newer and innovative concepts like Aptamers in therapy were discussed. One of the most exciting presentations in the conference came from Prof. Alan Perkins of UK, was based on the highly controversial topic of Plutonium poisoning.This was an extremely informative and useful presentation and hopefully served its purpose of creating awareness on the medical, social and legal implications of this extremely toxic and dangerous

  6. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    Missailidis, Sotiris [The Open University, Milton Keynes (United Kingdom). Dept. of Chemistry and Analytical Sciences]. E-mail: s.missailidis@open.ac.uk; Perkins, Alan [University of Nottingham (United Kingdom). Dept. of Medical Physics; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2008-12-15

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  7. In vivo distribution of vesicles loaded with radiopharmaceuticals: a study of different routes of administration

    The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces. (U.S.)

  8. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  9. Suggestions for radiopharmaceutical drug development in Korea focusing on FDA exploratory IND guideline

    Regulation for the radiopharmaceuticals should be reasonably different from that of other drugs. Radiopharmaceuticals are always used by compounding based on the doctor's order, have short half life and very low administration dose. Its pharmacological effect is not from its chemical effect but from radiation. The background for exploratory IND (Investigational New Drug) explained by the FDA was to reduce the time and resources expended on candidate products that are unlikely to succeed, new tools are needed to distinguish earlier in the process those candidates that hold promise from those that do not. In this review, basic concept for exploratory IND and RDRC guideline is summarized and various suggestions for improving and expediting procedure for new radiopharmaceutical development would be described

  10. Development of methodologies for internal exposure assessment due to the radiopharmaceutical 18FDG

    The production of 18F has increased in the last decade. It is produced basically for the synthesis of 18F- fluorodeoxyglucose (18FDG), the main radiopharmaceutical used in PET (Positron Emission Tomography) scans. The growth in the frequency of these tests resulted in rise of the number of occupationally exposed individuals (OEI) to the radionuclide 18F as 18FDG, increasing thereby the probability of its accidental incorporation. This study aimed to implement optimized techniques for assessing internal exposures of individuals occupationally exposed through both in vivo and in vitro bioassay methods during production and handling of 18FDG at the Divisao de Producao de Radiofarmacos (DIPRA), Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN). The in vivo monitoring was conducted at the Laboratorio de Dosimetria Interna, Divisao de Laboratorios Tecnico-Cientificos (DILAB). For this bioassay method, measurements were done with a 3x3' NaI(Tl) scintillation detector coupled to Genie 2000 software. The calibration of the system was performed with a brain phantom containing a standard liquid source of 22Na to simulate a contaminated individual. The calibration of the HPGe coaxial detector for in vitro monitoring was performed at the Laboratorio de Medidas de Atividade de Radionuclideos (DIPRA/CRCN-NE/CNEN) with a standard source of 22Na. Base on the calibration factors, it was possible to determine the minimum detectable activities (MDA) for the systems by using direct measurements and simulation of uncontaminated urine. Then, through the biokinetic models published by ICRP 106 and edited by the AIDE software (version 6.0), it was possible to estimate the minimum detectable effective dose (MDED), which evaluates the detection sensitivity of the techniques developed. The MDED was estimated for in vivo and in vitro measurements performed 2.4 hours after the occurrence of incorporation by ingestion, since this is the period of higher retention fraction of

  11. Development of Facilities and Provision of Radioisotope and Radiopharmaceutical Process based reactor GA Siwabessy

    The application of radioisotope technology, which is dynamically developing in Indonesia, needs to be compensated by the improvement of capacity and part of the CDRR in preparation and supply of GA Siwabessy-reactor-based radioisotopes and radiopharmaceuticals. On the other hand, the improvement of reactor-based radioisotope production capability will support and push the operational performance and function of the GA Siwabessy reactor facility. Implementation of radioisotope and radiopharmaceutical production capability should be successively joined with the readiness of supporting facility operational function in order to gain safety of the system, process, personnel and environment as well. The aging systems and facilities should be rejuvenated to keep maintenance their operational performance and function. By the reasons of those, some activities have been carried out covering services on operation and maintenance of supporting facilities, services on preparation of GA Siwabessy-reactor-based radioisotope and radiopharmaceutical products, and rejuvenation of chiller system that was gradually performed without disturbing the whole working function of the system. These activities are oriented into improvement of domestic radioisotope application for public welfare especially in the field of health, as well as gaining implementation of whole CDRR's programs safely and pleasantly. The outputs of the activities are merits (operational function, maintenance and repair of the systems and facilities), products (radioisotope and radiopharmaceutical preparations) and rejuvenation of facility. The results of work are quantitatively expressed in the total kinds or amounts of radioisotope and radiopharmaceutical products and the total operational hours of the facilities. Qualitatively, the result of works showed the continuity of readiness of supporting facilities as well as the continuity of services on preparation and supply of radioisotope and radiopharmaceutical

  12. Quality evaluation of radiopharmaceuticals in nuclear medicine services in the states of Alagoas and Sergipe - Brazil

    Santos, Poliane Angelo de Lucena; Andrade, Wellington Gomes de; Lima, Fernando Roberto de Andrade, E-mail: wandrade@cnen.gov.br, E-mail: falima@cnen.gov.br [Universidade Federal de Pernambuco (DEN/UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Lima, Fabiana Farias de, E-mail: fflima@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    Radiopharmaceuticals are compounds associated with a radionuclide. They can be considered as vectors that have some specificity for an organ or a physiological or pathophysiological function. Assessing the radiopharmaceutical's quality is essential to obtain adequate images, avoiding repetition of examinations and unnecessary absorbed dose to the patient. Resolution no. 8 (RCD 38) of 06/04/2008 by Agencia Nacional de Vigilancia Sanitaria (ANVISA) states the obligation of performing a minimum of tests in the routines of nuclear medicine services (NMS). The aim of this work was to evaluate the radiochemical purity and pH of radiopharmaceuticals used in NMS in states of Alagoas and Sergipe - Brazil. Radiochemical purity was determined by thin layer chromatography where a paper Whatman and TLC were used as steady state and the solvents were used related to the appropriate radiopharmaceutical, both as recommended by the manufacturer's directions. The chromatographic strips were placed in closed containers to avoid contact with the walls. After, the strips were cut in 1cm pieces and the activity was determined in each NMS's activity calibrators. The radiopharmaceuticals pH was evaluated by using universal pH paper (Merck) and the obtained color was compared with its range of colors. It was observed that 33.34% and 2.3% of the tested radiopharmaceuticals showed PRQ (radiochemical purity) and pH values, respectively, are outside of the limits described by the manufacturers. The results show that the radiochemical purity assessment in the NMS's routine can indicate problems with a radioisotope tagging, allowing their exclusion before administration. (author)

  13. Quality evaluation of radiopharmaceuticals in nuclear medicine services in the states of Alagoas and Sergipe - Brazil

    Radiopharmaceuticals are compounds associated with a radionuclide. They can be considered as vectors that have some specificity for an organ or a physiological or pathophysiological function. Assessing the radiopharmaceutical's quality is essential to obtain adequate images, avoiding repetition of examinations and unnecessary absorbed dose to the patient. Resolution no. 8 (RCD 38) of 06/04/2008 by Agencia Nacional de Vigilancia Sanitaria (ANVISA) states the obligation of performing a minimum of tests in the routines of nuclear medicine services (NMS). The aim of this work was to evaluate the radiochemical purity and pH of radiopharmaceuticals used in NMS in states of Alagoas and Sergipe - Brazil. Radiochemical purity was determined by thin layer chromatography where a paper Whatman and TLC were used as steady state and the solvents were used related to the appropriate radiopharmaceutical, both as recommended by the manufacturer's directions. The chromatographic strips were placed in closed containers to avoid contact with the walls. After, the strips were cut in 1cm pieces and the activity was determined in each NMS's activity calibrators. The radiopharmaceuticals pH was evaluated by using universal pH paper (Merck) and the obtained color was compared with its range of colors. It was observed that 33.34% and 2.3% of the tested radiopharmaceuticals showed PRQ (radiochemical purity) and pH values, respectively, are outside of the limits described by the manufacturers. The results show that the radiochemical purity assessment in the NMS's routine can indicate problems with a radioisotope tagging, allowing their exclusion before administration. (author)

  14. Modern trends in radiopharmaceuticals for diagnosis and therapy. Proceedings of a symposium

    The IAEA held an International Symposium on Modern Trends in Radiopharmaceuticals for Diagnosis and Therapy in Lisbon, Portugal, from 30 March to 3 April 1998. Two earlier symposia were organized on similar topics in Copenhagen, Denmark in 1973 and in Tokyo, Japan, in 1984. The proceedings of these symposia have been published and widely used as reference sources. To facilitate faster publication and more widespread availability, the IAEA has decided to publish the proceedings of this symposium as a cost-free TECDOC. The symposium was organized into 14 sessions consisting of five on 99mTc radiopharmaceuticals, two each on therapeutic radiopharmaceuticals and radiohalogens/other isotopes and one each on bioevaluation, radiometric assay, medical isotope production, good radiopharmacy practice and technology transfer. In the proceedings the papers from multiple sessions on the same topic have been grouped together for the convenience of the reader. The papers presented in the symposium reflect current and future developments in diagnostic and therapeutic agents. The largest number of papers presented dealt with 99mTc, highlighting its continuing importance to nuclear medicine and the role of imaging as an important tool. The emerging interest in therapeutic radiopharmaceuticals based on beta emitting short lived isotopes such as 186Re and 153Sm was evident from the papers presented in two sessions devoted to this topic. Also of steady interest was the development of agents labelled with other established isotopes, radioiodine in particular and also 111In and 67Ga. Regulation, training and good manufacturing practices are important for ensuring safety in regular use of radiopharmaceuticals and were discussed in a separate session. The production of radiopharmaceuticals has become a regular activity in many developing countries, often facilities were presented at the symposium

  15. Post-target produced [18F]F2 in the production of PET radiopharmaceuticals

    Electrophilic radiofluorination was successfully carried out in the early years of PET radiochemistry due to its ease and fast reaction speed. However, at the present, the use of electrophilic methods is limited due to low specific activity (SA). Post-target produced [18F]F2 has significantly higher SA compared to other electrophilic approaches, and it has been used in the production of clinical PET radiopharmaceuticals at the Turku PET Centre for years. Here, we summarize the synthesis and use of these radiopharmaceuticals, namely [18F]FDOPA, [18F] CFT, [18F]EF5 and [18F]FBPA.

  16. Evaluation of radiochemistry purity and p H of radiopharmaceuticals in nuclear medicine services at Pernambuco, Brazil

    Radiopharmaceuticals are cellular or molecular structures that have a radionuclide in its composition and they are used for diagnosing or treating diseases. The evaluation of the radiochemical purity of radiopharmaceuticals is essential to produce images with artifacts free, as well as avoid unnecessary absorbed dose to the patient. Since they are administered in humans is important and necessary that they undergo rigorous quality control. Due to this fact, the norm in ANVISA RDC 38/2008 declaring the mandatory completion of a minimum of tests in routine nuclear medicine services before human administration. (author)

  17. A 3D high-resolution gamma camera for radiopharmaceutical studies with small animals

    Loudos, G K; Giokaris, N D; Styliaris, E; Archimandritis, S C; Varvarigou, A D; Papanicolas, C N; Majewski, S; Weisenberger, D; Pani, R; Scopinaro, F; Uzunoglu, N K; Maintas, D; Stefanis, K

    2003-01-01

    The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2 mm in planar and 2-3 mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.

  18. What Lies Within: Using Radiopharmaceuticals to Reveal and Target Diseases Hidden Inside the Human Body

    The ability to pinpoint the location and size of a cancerous mass hidden inside of a patient’s body was unthinkable less than 100 years ago. Today, with the help of special scanning machines, doctors are able to use radioactive drugs known as radiopharmaceuticals to get a glimpse inside the human body, and these pharmaceuticals can even be used in treating many health conditions. In nuclear medicine, radiopharmaceuticals play an essential role for minimally invasive diagnostic, treatment and care management procedures for many diseases, especially cancer, as well as for relieving pain associated with certain cancers

  19. Study on design of GMP facility for radio-pharmaceuticals production

    For production and research for practical use of radio-pharmaceuticals using for medical treatment and diagnosis, the complex facility offer shield and clean environment is basically required for protecting personnel from radiation, and protecting the product from contamination. This facility should be designed to comply with GMP(Good Manufacturing Practice). In this study, technical requirements and guide for hot cell and clean room were investigated, and design concept and requirements of facility for radio-pharmaceuticals handling are suggested. And also, GMP facility for production of Tc-99m generator and other radio-pharmaceuticals(Ho-166 etc.) was designed to comply with this design concept and requirements

  20. Radiopharmaceuticals for diagnosis. [Final] report, 1 January 1991--31 December 1993

    Kuhl, D.E.

    1993-06-01

    Since 1987, this grant has supported the development of new radiochemical methods for use with short-lived, positron-emitting radionuclides; new laboratory techniques for radiochemical syntheses; and development of new radiopharmaceuticals which will be of use in Positron Emission Tomography. For the period 1 January 1991 to 31 December 1993, the authors have continued their efforts in all of these areas, as they feel that an integrated approach to the synthesis and characterization of new PET Radiopharmaceuticals is crucial to the continued growth and application of this imaging technique in modern medicine. Progress in a number of these areas is described in this report.

  1. Determination and reliability of dose coefficients for radiopharmaceuticals; Ermittlung der Zuverlaessigkeit von Dosiskoeffizienten fuer Radiopharmaka

    Spielmann, V.; Li, W.B.; Zankl, M.; Oeh, U.

    2015-11-15

    The dose coefficients used in nuclear medicine for dose calculations of radiopharmaceuticals are based on recommendations by ICRP (International Commission on radiological protection) and the MIRD (Medical Internal Radiation Dose Committee) using mathematical models for the temporal activity distributions in organs and tissues (biokinetic models) and mathematical models of the human body. These models using an idealized human body do not include uncertainty estimations. The research project is aimed to determine the uncertainties and thus the reliability of the dose coefficients for radiopharmaceuticals and to identify the biokinetic and dosimetric parameters that contribute most of the uncertainties.

  2. The challenges of handling an ever increasing volume of radiopharmaceuticals by air - A case study

    Transporting radiopharmaceuticals by air is more than just putting a box on an aircraft. Many other factors need to be taken into consideration, primarily the health and safety of the airline staff coming into contact with the shipments, the requirements of the shipper and the needs of the end user. With a thorough understanding of the radiopharmaceutical industry, airlines can work in partnership with manufactures to provide the levels of service required to sustain the industry. The consultation and involvement with employees in developing workable procedures is also critical to the success of the handling process. (author)

  3. Incorporation of radiohalogens via versatile organometallic reactions: applications in radiopharmaceutical chemistry

    Srivastava, P.C.; Goodman, M.M.; Knapp, F.F. Jr.

    1985-01-01

    Factors that must be considered for the design of radiohalogenated radio-pharmaceuticals include the stability and availability of the substrate, the physical half-life of the radiohalogen and the in vivo stability of the radiolabel. Vinyl and phenyl radiohalogen bonds show more in vivo stability than the alkyl radiohalogen bonds. Consequently, a variety of methods suitable for the synthesis of tissue specific radiopharmaceuticals bearing a vinyl or phenyl radiohalogen have been developed involving the synthesis and halogenation of metallovinyl and phenyl intermediates. The halogens and metallation reactions include iodine and bromine and alanation, boronation, mercuration, stannylation, and thallation, respectively. 19 refs., 1 fig., 1 tab.

  4. MAFIA Version 4

    Weiland, T.; Bartsch, M.; Becker, U.; Bihn, M.; Blell, U.; Clemens, M.; Dehler, M.; Dohlus, M.; Drevlak, M.; Du, X.; Ehmann, R.; Eufinger, A.; Gutschling, S.; Hahne, P.; Klatt, R.; Krietenstein, B.; Langstrof, A.; Pinder, P.; Podebrad, O.; Pröpper, T.; van Rienen, U.; Schmidt, D.; Schuhmann, R.; Schulz, A.; Schupp, S.; Schütt, P.; Thoma, P.; Timm, M.; Wagner, B.; Weber, R.; Wipf, S.; Wolter, H.; Min, Z.

    1997-02-01

    MAFIA Version 4.0 is an almost completely new version of the general purpose electromagnetic simulator known since 13 years. The major improvements concern the new graphical user interface based on state of the art technology as well as a series of new solvers for new physics problems. MAFIA now covers heat distribution, electro-quasistatics, S-parameters in frequency domain, particle beam tracking in linear accelerators, acoustics and even elastodynamics. The solvers that were available in earlier versions have also been improved and/or extended, as for example the complex eigenmode solver, the 2D-3D coupled PIC solvers. Time domain solvers have new waveguide boundary conditions with an extremely low reflection even near cutoff frequency, concentrated elements are available as well as a variety of signal processing options. Probably the most valuable addition are recursive sub-grid capabilities that enable modeling of very small details in large structures.

  5. MAFIA Version 4

    Weiland, T. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Bartsch, M. [CST Computer Simulations Technology GmbH, Lauteschlaegerstr. 38, D64289 Darmstadt (Germany); Becker, U.; Bihn, M. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Blell, U. [GS1 mbH, Planckstr. 1, 64291 Darmstadt (Germany); Clemens, M.; Dehler, M. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Dohlus, M. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany)]|[Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, D22607 (Germany); Drevlak, M. [Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, D22607 (Germany); Du, X. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Ehmann, R.; Eufinger, A. [CST Computer Simulations Technology GmbH, Lauteschlaegerstr. 38, D64289 Darmstadt (Germany); Gutschling, S. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Hahne, P. [CST Computer Simulations Technology GmbH, Lauteschlaegerstr. 38, D64289 Darmstadt (Germany); Klatt, R.; Krietenstein, B.; Langstrof, A.; Pinder, P.; Podebrad, O.; Proepper, T.; van Rienen, U.; Schmidt, D.; Schuhmann, R. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Schulz, A. [CST Computer Simulations Technology GmbH, Lauteschlaegerstr. 38, D64289 Darmstadt (Germany); Schupp, S.; Schuett, P.; Thoma, P.; Timm, M. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Wagner, B. [CSS Computer Simulation Services GbRmbH, Lauteschlaegerstr. 38, D64289 Darmstadt (Germany); Weber, R. [AET Inc., 1-1-7 Mukaibara, Asaoku, Kawasaki City (Japan); Wipf, S. [Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, D22607 (Germany); Wolter, H. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany); Min, Z. [TH-Darmstadt, Fachbereich 18, Schlossgartenstr.8, D64289 Darmstadt (Germany)

    1997-02-01

    MAFIA Version 4.0 is an almost completely new version of the general purpose electromagnetic simulator known since 13 years. The major improvements concern the new graphical user interface based on state of the art technology as well as a series of new solvers for new physics problems. MAFIA now covers heat distribution, electro-quasistatics, S-parameters in frequency domain, particle beam tracking in linear accelerators, acoustics and even elastodynamics. The solvers that were available in earlier versions have also been improved and/or extended, as for example the complex eigenmode solver, the 2D--3D coupled PIC solvers. Time domain solvers have new waveguide boundary conditions with an extremely low reflection even near cutoff frequency, concentrated elements are available as well as a variety of signal processing options. Probably the most valuable addition are recursive sub-grid capabilities that enable modeling of very small details in large structures. {copyright} {ital 1997 American Institute of Physics.}

  6. Development of Radiopharmaceuticals for effective use of PET

    The most contribution of PET popularization is tumor diagnosis with 18F-FDG. It can detect various tumors with high sensitivity and specificity, so utility of PET with 18F-FDG are undoubted in tumor diagnosis. Although the development of new radiopharmaceuticals for tumor diagnosis is proceeding such as [ 18F]3-deoxy-3'-fluorothymidine (FLT), [18F-alpha-methyl]tyrosine (FAMT), etc., among these compounds, it is very interesting subject that which one can become superior to 18F-FDG, or supplement it. On the other hand, PET is the most attractive technique for the drug company, because PET can evaluate in vivo kinetics of drugs directly. Until now, in the development of drugs, objective evaluation of drugs action might be difficult, and kinetics of drugs can be estimated only from the concentration in blood and urine. PET can indicate directly how the drug reaches the action site, how it should be administered to obtain the action, and how it shifts to other organs. It becomes very useful information for the development and evaluation of drugs. PET may facilitate the drug development, and it has the possibility of adequate evaluation of drugs. In the nuclear medicine current researches, application of PET for imaging of small animals has been interested according to the advance of PET camera resolution. The small animal imaging is useful technique in the investigation of various diseases and the development of drugs, because it can evaluate the detailed information from the same animal and time after time. Especially, from the beginning of PET history, research has been mainly focused on the study of brain function. So, in the research of neurological and neuropsychiatric disorder, such as Alzheimer's disease or depression. PET can be expected to find useful information. For these diseases, analysis of nicotinic acetylcholine receptor with A-85380 (3-[2(S)-azetidinylmethoxy]pyridine) derivatives and serotonin transporter with [11CJ-3-amino∼4-(2-dimethylaminomethyl

  7. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  8. Development of more efficacious Tc-99m organ imaging agents for use in nuclear medicine by characterization of radiopharmaceuticals. Final report, September 1, 1992--June 30, 1998

    The primary goals of this project were twofold: (1) Development of a microsensor that would demonstrate the capability for in vivo monitoring of a radiopharmaceutical after its injection into a test animal; and (2) Exploration of capillary electrophoresis (CE) as a separation technique for the analysis of radiopharmaceuticals that are mixtures of different compounds. The combination of in vivo sensors for real-time monitoring of specific chemical states of a radiopharmaceutical in individual organs and CE for analysis of radiopharmaceuticals prior to injection would provide valuable information regarding the fate of an imaging agent after administration. Such information should give insight into strategies for the development of more efficacious radiopharmaceuticals

  9. Axodraw Version 2

    Collins, John C

    2016-01-01

    We present version two of the Latex graphical style file Axodraw. It has a number of new drawing primitives and many extra options, and it can now work with \\program{pdflatex} to directly produce output in PDF file format (but with the aid of an auxiliary program).

  10. Results of the quality assurance testing programme for radiopharmaceuticals 1984-1985

    The Australian Radiation Laboratory conducts a Radiopharmaceutical Quality Assurance Test Programme in which radiopharmaceuticals used in nuclear medicine in Australia are tested for compliance with specifications. Samples obtained for testing were obtained through normal commercial channels. All technetium-99m cold kits were reconstituted according to the directions in the package insert using sodium pertechnetate (99mTc) B.P. The results of testing during 1984 and 1985 are summarised. Overall, 215 batches of 28 different types of radiopharmaceutical were tested in 1984-5. Failure to meet full specifications was observed in 26 of the 215 batches of radiopharmaceuticals tested (12.0%). Labelling errors were observed in 14 of the 26 batches failing specifications and was solely responsible for the failure of the product on 13 of these occasions. Most other failures were due to either the incorrect radionuclide activity being provided or the radiochemical purity being less than that required in the specifications. A section has also been included on the technetium-99 content of the sodium pertechnetate (99Tc) injection. These results indicate that technetium-99 levels vary over a wide range and are present at about 7-8 times the level found in the fresh eluate from a chromatographic generator. At present, there is no specification for permissible levels of technetium-99. Users, however, should be aware of the effects of these increased levels in some labelling applications e.g. blood cells or monoclonal antibodies

  11. Design of CGMP Production of 18F- and 68Ga-Radiopharmaceuticals

    Yen-Ting Chi

    2014-01-01

    Full Text Available Objective. Radiopharmaceutical production process must adhere to current good manufacturing process (CGMP compliance to ensure the quality of precursor, prodrug (active pharmaceutical ingredient, API, and the final drug product that meet acceptance criteria. We aimed to develop an automated system for production of CGMP grade of PET radiopharmaceuticals. Methods. The hardware and software of the automated synthesizer that fit in the hot cell under cGMP requirement were developed. Examples of production yield and purity for 68Ga-DOTATATE and 18F-FDG at CGMP facility were optimized. Analytical assays and acceptance criteria for cGMP grade of 68Ga-DOTATATE and 18F-FDG were established. Results. CGMP facility for the production of PET radiopharmaceuticals has been established. Radio-TLC and HPLC analyses of 68Ga-DOTATATE and 18F-FDG showed that the radiochemical purity was 92% and 96%, respectively. The products were sterile and pyrogenic-free. Conclusion. CGMP compliance of radiopharmaceuticals has been reviewed. 68Ga-DOTATATE and 18F-FDG were synthesized with high radiochemical yield under CGMP process.

  12. A study of effluent control technologies employed by radiopharmaceutical users and suppliers

    The quantities of radiopharmaceuticals produced for in-vivo diagnostic and therapy procedures has been estimated to be growing at the rate of 16% per year, based on 1978 sales figures. Nuclear medicine facilities are experiencing an average annual growth rate of 5% per year. The principle radionuclides produced and used for nuclear medicine are 131I, 131Xe, and sup(9m)Tc. Of particular concern is that amount of these radionuclides which might become airborne and escape into the environment during the process of manufacture or during aliquotting or administration by hospital personnel. Therefore, a study was made of the effluent control technology employed by radiopharmaceutical suppliers and users. Generally, the means used to control airborne radioactive effluents fall into two classes according to function. The controls either dilute and direct the effluent to a specific point of release or hold up the effluent to reduce by decay the amount of radioactivity released. Radiopharmaceutical suppliers and hospitals were contacted, and a survey made of the control technology used. The classes and types of effluent control equipment and their general characteristics, cost and effectiveness were determined. It was concluded that control equipment was readily available, reliable, and effective in reducing radioactive releases from radiopharmaceutical facilities. (author)

  13. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1980-December 31, 1981

    Although the germanium-68 → gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available 68Ga/68Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than 68Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing 68Ga-radiopharmaceuticals. Several years ago, we developed a new generator using a solvent extraction system which produces 68Ga-oxine (8-hydroxyquinoline), a weak chelate. We have also carried out studies to compare generator systems which produce 68Ga in an ionic form. Using the gallium-68 eluted from these various generator systems, several 68Ga-labeled radiopharmaceuticals have been synthesized and tested in vitro and in vivo. In addition, attempts have been made to design and synthesize a lipophilic ligand for gallium-68. The stability of radiogallium complexed with a series of potentially lipophilic complexing agents has been studied using chromatographic techniques and in vivo distribution data. The potential of these complexing agents for altering the biodistribution of gallium radiopharmaceuticals has also been investigated

  14. Acquisition of biokinetic data for internal dose calculations for some novel radiopharmaceuticals

    Estimation of radiation dose commitment, expresses as an effective dose equivalent, is a prior requisite to the application for a license to administer radiopharmaceuticals and, therefore, in the case of novel radiopharmaceuticals is leading to an increasing awareness of the need for dosimetry-orientated studies. In this laboratory potential new radiopharmaceuticals are investigated initially by animal studies to assess the possible distribution in man, and subsequently in controlled volunteer studies designed to obtain the maximum possible amount of biokinetic data to allow accurate estimation of radiation dose. A variety of techniques are used for this purpose, including profile counting, partial and whole-body scanning by LFOV gamma camera and whole-body counting, in addition to the analysis of radioactivity in blood and excreta. The use of these techniques is illustrated for the acquisition of biokinetic data and subsequent dosimetry of three novel radiopharmaceuticals: 77Br-p-bromospiperone (quantification of dopamine receptors in the brain). 99Tc/sup m/-porphyrins and 99Tc/sup m/ DEPE (a possible novel blood pool marker for MUGA studies). 14 references, 14 figures, 2 tables

  15. Radiolabeling of human platelets using four radiopharmaceuticals with Tc-99m

    The present investigation work has been done in an evaluation of four different radiopharmaceuticals with Tin II (Glucoheptonate, Pyrophosphate, Citrate and DTPA), with the purpose of determining which one of the four would be obtained a higher rate of radiolabeling of platelets with Tc-99m. In order to evaluate the four radiopharmaceuticals it was procede to the separation and labeling of the human platelets. It was worked with samples of blood from five pacients, and the platelets from each one of them were labeled with the radiopharmaceuticals-Tc-99m. Then was observed a significant difference among the four radiopharmaceuticals studied, with a reliable level of 0.05 being the Glucoheptonate-Tc-99m the best to label platelets, obtaining with the same 50.23% of labeling efficiency, while for DTPA, Pyrophosphate and Citrate, It was obtained 33.42%, 29.82% and |2.62% respectively. Also, it was studied the biodistribution of the labeled platelets, using Glucoheptonate-Tc-99m as a radiopharamceutical. The biodistribution was studied in white mice at different times and it was founded that the place of biodistribution of the labeled platelets is given in greater percentage in the liver, spleen, lungs and kydneis. (Author)

  16. A remote system for the routine production of oxygen-15 radiopharmaceuticals

    The details of the construction and operation of a remote, automated system for the production of oxygen-15 labelled radiopharmaceuticals are described. This system routinely provides oxygen-15 labelled oxygen, carbon monoxide, and water directly to the PET imaging facility, in quantities and purities suitable for human studies. (author)

  17. The quality control of technetium-99m radiopharmaceuticals produced at the AAEC Research Establishment

    The methods of quality control used for technetium-99m radiopharmaceuticals produced at the AAEC Research Establishment are described for both non-fission and fission derived sources of sodium pertechnetate, technetium-99m labelled radipopharmaceuticals, and reagent kits produced for technetium-99m labelling

  18. Validation of the method for investigation of radiopharmaceuticals for in vitro use

    The aim of this study was to validate analytical method for determination of total radioactivity and radioactive concentration of 125I-triiodotironin, radiopharmaceutical for in vitro use. Analytical parameters: selectivity, accuracy, linearity and range of this method were determined. Values obtained for all parameters are reasonable for analytical methods, therefore this method could be used for farther investigation. (author)

  19. Tracers to monitor the response to chemotherapy: in vitro screening of four radiopharmaceuticals.

    Geus-Oei, L.F. de; Eerd-Vismale, J.E.M. van; Molthoff, C.F.M.; Corstens, F.H.M.; Oyen, W.J.G.; Boerman, O.C.

    2004-01-01

    OBJECTIVES: It has been postulated that radiopharmaceuticals can be used to predict the therapeutic response to (chemo)therapy, which could lead to individualized treatment regimens. In this study, 18F-deoxyglucose, 99mTc-tetrofosmin, 125I-deoxyuridineribose, and 125I-methyltyrosine were tested for

  20. Biological evaluation of 175Yb-EDTMP as radiopharmaceutical for bone pain palliation

    Ideal radiopharmaceutical used as bone pain palliatives requires a moderate energy β emitter with a stable carrier molecule. Ytterbium-175 (T1/2 = 4.2 d, Eβ(max) = 0,480 MeV) has radionuclide properties suitable for palliative therapy of bone metastases. Ethylenediamine tetramethylene phosphonic acid (EDTMP) is known to form complexes with high stability. The present study was conducted to evaluate EDTMP complexed with 175Yb as radiopharmaceutical for bone imaging and potential agents for bone palliation which produced by PTNBR-BATAN Bandung. The 175Yb-EDTMP radiopharmaceutical was tested for the biodistribution and blood clearance. The bone uptake of 175Yb-EDTMP complexes are 12.68; 11.83; 10.00; and 8.20 (%ID) at 1, 3, 5 and 24 h post-injection. The radioactivity level in the stomach was 0.06 (%ID/g) up to 24 h post-injection, indicating that 175Yb-Emptied remained stable in vivo. The blood clearance study exhibited that 175Yb-Emptied had fast clearence profile from blood.This study showed that 175Yb-EDTMP is potential as radiopharmaceutical for bone pain palliation agents. (author)

  1. Obligations, precautions and pending issues in regulatory development for radiopharmaceuticals in Brazil

    Radiopharmaceuticals are compounds that have a radionuclide and may be gamma-radiation emitter (γ) or positrons emitter (β+), linked to a molecule with specific diagnostic and therapeutic purposes. The progress in the use of radiopharmaceuticals has culminated to a sector in common with other types of drugs: regulation and surveillance. >From 2006 on, production, marketing and use of these drugs were open to the Brazilian market granting much more freedom due to the Constitutional Amendment 49, resulting from the previous Constitutional Amendment 199/03 which removes the Union monopoly for this kind of manipulation and granted this production to other nuclear medicine. From this date on, the amount of this type of sold product have been greatly increased, and the nucleus of surveillance and regulation in Brazil have also advanced in the legislative processes, creating documents that are now more focused on radiopharmaceuticals in the national territory (Resolutions No. 63 and No. 64). In international overview, there is too much to be done in regulatory terms in Brazil, such as adding mainly issues of drugs surveillance to pharmacovigilance practice in radiopharmaceuticals drugs. (author)

  2. Studies on quality assurance in the determination of activities of radiopharmaceuticals in nuclear medicine

    The activity of radiopharmaceuticals is routinely measured by activimeters (radionuclide calibrators) calibrated for radionuclides relevant to nuclear medicine. In this work the influence of the measurement conditions (measuring geometry, sample type, radionuclidic impurities) on the activity value indicated by these instruments is studied quantitatively. Round robins for several radionuclides show what uncertainties are found in practical activity measurements. (orig.)

  3. Determination of Sn in 99mTc Radiopharmaceutical Kits by Polarographic Methods

    Kits of 99mTc radiopharmaceuticals are used in nuclear medicine for diagnosis of different diseases. Sn (II) is one of the essential components in their formulations, which is used for reduction 99mTc-pertechnetate in cold kits for on-site preparation 99mTc-pertechnetate radiopharmaceuticals. Usually, these cold kits contain different additives (complexing agents, antioxidants, buffers, etc.) and the amount of Sn (II) varies from kit to kit. The determination of Sn in these products is essential in assessing their quality. We report here the development of a new polarographic method for the determination of Sn (II) and total Sn in representative radiopharmaceuticals kits (for the content of Sn and chemical composition) produced at the Center of Isotopes of Cuba (CENTIS). These methods were validated by analysis of variance and recovery techniques. From the results of the validation, the characteristic functions of uncertainties and fits are considered for the established methods, which give the necessary evidences to demonstrate the usefulness of these methods according to the current trends in Analytical Chemistry. This work provides practical results of great importance for CENTIS. After the speciation of Sn in the MAG3 radiopharmaceuticals kit is inferred that the production process is affected by uncontrolled factors that influence in the product stability, which demonstrates the necessity for analytical tools for the characterization of products and processes. (Author) 57 refs.

  4. Production of radionuclides and radiopharmaceuticals at the Argentine Atomic Energy National Commission

    The production of radionuclides and radiopharmaceuticals at the CNEA is described, as well as the preparation of reagent's sets, and informations is given on the preparation of Tc-99m and In-113m generators. Some figures of the production of 1974-1976 are given. (author)

  5. The study on the use of fragmented antibody for the development of therapeutic radiopharmaceutical

    This project was designed to develop the therapeutic radiopharmaceuticals for therapy and diagnosis of cancer using fragmented antibodies. The major activities to be carried out are as follows: - exploration of the key angiogenic factors involved in cancer, - development of radiolabeled-compounds using antibody fragments for minimal toxicity - In vitro/vivo investigation on the targeting ability of RI labeled antibody fragment

  6. Obligations, precautions and pending issues in regulatory development for radiopharmaceuticals in Brazil

    Gamboa, Maryelle Moreira Lima; Roesch, Heveline Rayane Moura; Lemos, Vanessa Pinheiro Amaral, E-mail: maryellelg@hotmail.com [PPG BioSaude, Universidade Luterana do Brasil, Canoas, RS (Brazil); Rocha, Bruna Oliveira [Faculty of Biology, Universidade Luterana do Brasil, Canoas, RS (Brazil); Santos-Oliveira, Ralph [Institute of Radiopharmacy Research, Universidade Estadual da Zona Oeste, Rio de Janeiro, RJ (Brazil)

    2014-04-15

    Radiopharmaceuticals are compounds that have a radionuclide and may be gamma-radiation emitter (γ) or positrons emitter (β+), linked to a molecule with specific diagnostic and therapeutic purposes. The progress in the use of radiopharmaceuticals has culminated to a sector in common with other types of drugs: regulation and surveillance. >From 2006 on, production, marketing and use of these drugs were open to the Brazilian market granting much more freedom due to the Constitutional Amendment 49, resulting from the previous Constitutional Amendment 199/03 which removes the Union monopoly for this kind of manipulation and granted this production to other nuclear medicine. From this date on, the amount of this type of sold product have been greatly increased, and the nucleus of surveillance and regulation in Brazil have also advanced in the legislative processes, creating documents that are now more focused on radiopharmaceuticals in the national territory (Resolutions No. 63 and No. 64). In international overview, there is too much to be done in regulatory terms in Brazil, such as adding mainly issues of drugs surveillance to pharmacovigilance practice in radiopharmaceuticals drugs. (author)

  7. Radio-pharmaceuticals for human use: the legal framework and the clinical indications authorised in Spain

    The inclusion of radio-pharmaceuticals in the health legislation represented a significant change because of the obligation, for the first time, to undergo a registration process to enable them to be marketed. It also served to regulate clinical investigation using these drugs, and the prior evaluation they must undergo in other to obtain official health clearance. (Author) 27 refs

  8. A Study on the Quality Control of 18F-FDG Radiopharmaceutical

    The types of test items which were recorded in this test report of quality control domestic 18F-FDG radiopharmaceutical which consisted of 13 different types: appearance, half-life, radioactive heterokaryosis, radiochemical Confirmation (measure of Rf value), radiochemical Purity, Ethanol, Acetonitrile, Kryptofix, Aluminium, pH, Endotoxin, aseptic test, and radioactivity·ml-1. The record was fully recorded in 'appearance', 'radioactive heterokaryosis', 'pH', 'Endotoxin', and 'aseptic test'. In 'half-life', 'radiochemical Confirmation (measure of Rf value), 'radiochemical Purity', 'Ethanol', 'Acetonitrile', 'Kryptofix', 'Aluminium', 'radioactivity·ml-1', there were differences in records of each manufacturing business on radioactive medicine and medical supplies. The result of the test showed all 13 items of quality control test were 100% suitable on the basis of recorded data. There were more radiopharmaceutical made in the laboratory than in hospitals and businesses and in for result of suitability test, the laboratory showed higher suitability than did the hospitals or businesses. Domestically, there are differences of the test report items in the safety of radiopharmaceutical of each facility, and since it is not standardized, supplements are needed. To submit standardized test reports of quality guarantee in radiopharmaceutical, GMP of U.S. and CE Mark of Europe should be referred as well as receiving advice from professionals to standardize as suitable domestic standard

  9. Method for preparing 99mTc-labelled radiopharmaceuticals for myocardial scintigraphy

    Radiopharmaceuticals which preferably concentrate in myocardial tissue are prepared, in particular technetium compounds with the reducing ligand molecule DMPE. A method is introduced to convert pertechnetate in one step into the proposed compound by means of a saline, slow-oxidizing and lyophilized form of the reducing ligand DMPE, preferably DMPE x 2HCl

  10. Information manual on the microbiological aspects of good manufacturing practices for radiopharmaceutical preparations

    A description is given of clean air units, clean room garments, disinfectants and types of contamination likely to affect radiopharmaceutical preparations and measures for their control. Specific precautions for the manufacture at Lucas Heights of sterile, pyrogen-free injectables and oral preparations of low microbial contamination are described

  11. New radiopharmaceuticals for adrenal scanning: radioiodine labelled tyramine derivates of heart glycosides and the respective aglycons

    In order to avoid certain disadvantages of the test substances for adrenal scanning currently being used, new radiopharmaceuticals - hydroxyphenylethylamine derivatives from digitalis glycosides - were synthesized, radioiodine-labelled and tested scintigraphically in animal experiments. The new compounds have been shown to be very appropriate, and it can be expected that they are well suited for clinical purposes especially when labelled by 123Iodine. (orig.)

  12. Harvard-MIT research program in short-lived radiopharmaceuticals. Technical progress report, 1991

    Adelstein, S.J.

    1991-12-31

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  13. Novel technetium chemistry and radiopharmaceuticals: Tc(V), Tc(III) or Tc(I) - Which way to go for keeping Tc radiopharmaceuticals alive?

    Novel 99mTc based radiopharmaceuticals which have found market introduction are rare. Despite enormous research efforts over the past 10 years, only very few new compounds (99mTc or 188Re) contribute to public health. New radiopharmaceuticals may belong to the class of perfusion or targeting agents in which a complex is conjugated to a receptor binding molecule. While other techniques are developing very rapidly, 99mTc based radiopharmacy risks losing its leading role in nuclear medicine to PET or MRI. Despite the authors' pessimistic view for the future of 99mTc research, 186Re. 188Re and other therapeutic radionuclides will fuel research in group 7 chemistry. Of course, many scientific papers can still be produced (which is as important as finding a novel radiopharmaceutical), but the ultimate goal should be the contribution to public health. The question arises as to why the situation is as described and how it can be changed (rapidly). This paper aims at a critical review of the limitations and requirements demanded for finding a novel radiopharmaceutical. The main focus here will be put on the underlying chemistry. Research in radiopharmaceutical chemistry should follow a 'top-down' strategy, to meet requirements from the market and production in clinics. Synthons are required for this drug finding process. Currently, 4 or 5 precursors are available, namely [Tc=O]3+, [TcO2]+ and [Tc≡N]2+ core from Tc being in the oxidation state +V, Tc(III) chemistry and [Tc(CO)3]+ chemistry in the +I valency. The HYNIC approach represents another strategy but suffers from an as yet undefined core. All of these approaches are likely to be successful from a coordination chemistry point of view. The presentation will critically emphasize their weak and strong points with regard to different kinds of biomolecules. The search for novel cores and strategies is not at its end and a number of hypothetical cores and methodologies will be proposed to complement the available ones

  14. Implementation of a metrology programme to provide traceability for radionuclides activity measurements in the CNEN Radiopharmaceuticals Producers Centers

    The commercialization and use of radiopharmaceuticals in Brazil are regulated by Agencia Nacional de Vigilancia Sanitaria (ANVISA) which require Good Manufacturing Practices (GMP) certification for Radiopharmaceuticals Producer Centers. Quality Assurance Program should implement the GMP standards to ensure radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled within the Quality Assurance Programs, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. The quality assurance of activity measurements is fundamental to maintain both the efficiency of the nuclear medicine procedures and patient and exposed occupationally individuals safety. The radiation doses received by patients, during the nuclear medicine procedures, is estimated according to administered radiopharmaceuticals quantity. Therefore it is very important either the activity measurements performed in radiopharmaceuticals producer centers (RPC) as the measurements performed in nuclear medicine services are traceable to national standards. This paper aims to present an implementation program to provide traceability to radionuclides activity measurements performed in the dose calibrators(well type ionization chambers) used in Radiopharmaceuticals Producer Center placed in different states in Brazil. The proposed program is based on the principles of GM Pand ISO 17025 standards. According to dose calibrator performance, the RPC will be able to provide consistent, safe and effective radioactivity measurement to the nuclear medicine services. (author)

  15. Implementation of a metrology programme to provide traceability for radionuclides activity measurements in the CNEN Radiopharmaceuticals Producers Centers

    Andrade, Erica A.L. de; Braghirolli, Ana M.S.; Tauhata, Luiz; Gomes, Regio S.; Silva, Carlos J., E-mail: erica@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Delgado, Jose U.; Oliveira, Antonio E.; Iwahara, Akira, E-mail: ealima@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    The commercialization and use of radiopharmaceuticals in Brazil are regulated by Agencia Nacional de Vigilancia Sanitaria (ANVISA) which require Good Manufacturing Practices (GMP) certification for Radiopharmaceuticals Producer Centers. Quality Assurance Program should implement the GMP standards to ensure radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled within the Quality Assurance Programs, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. The quality assurance of activity measurements is fundamental to maintain both the efficiency of the nuclear medicine procedures and patient and exposed occupationally individuals safety. The radiation doses received by patients, during the nuclear medicine procedures, is estimated according to administered radiopharmaceuticals quantity. Therefore it is very important either the activity measurements performed in radiopharmaceuticals producer centers (RPC) as the measurements performed in nuclear medicine services are traceable to national standards. This paper aims to present an implementation program to provide traceability to radionuclides activity measurements performed in the dose calibrators(well type ionization chambers) used in Radiopharmaceuticals Producer Center placed in different states in Brazil. The proposed program is based on the principles of GM Pand ISO 17025 standards. According to dose calibrator performance, the RPC will be able to provide consistent, safe and effective radioactivity measurement to the nuclear medicine services. (author)

  16. Current status of production and research of radioisotopes and radiopharmaceuticals in Indonesia

    Soenarjo, Sunarhadijoso; Tamat, Swasono R. [Center for Development of Radioisotopes and Radiopharmaceuticals, National Nuclear Energy Agency (BATAN), Kawasan Puspiptek, Serpong, Tangerang (Indonesia)

    2000-10-01

    The use of radioactive preparation in Indonesia has sharply increased during the past years, indicated by increase of the number of companies utilizing radioisotopes during 1985 to 1999. It has been clearly stressed in the BATAN's Strategic Plan for 1994-2014 that the production of radioisotopes and radiopharmaceuticals is one of five main industrial fields within the platform of the Indonesian nuclear industry. Research programs supporting the production of radioisotopes and radiopharmaceuticals as well as development of production technology are undertaken by the Research Center for Nuclear Techniques (RCNT) in Bandung and by the Radioisotope Production Center (RPC) in Serpong, involving cooperation with other research center within BATAN, universities and hospitals as well as overseas nuclear research institution. The presented paper describes production and research status of radioisotopes and radiopharmaceuticals in Indonesia after the establishment of P.T. Batan Teknologi in 1996, a government company assigned for activities related to the commercial application of nuclear technology. The reviewed status is divided into two short periods, i.e. before and after the Chairman Decree No. 73/KA/IV/1999 declaring new BATAN organizational structure. Subsequent to the Decree, all commercial requests for radioisotopes and radiopharmaceuticals are fulfilled by P.T. Batan Teknologi, while demands on novel radioactive preparations or new processing technology, as well as research and development activities should be fulfilled by the Center for the Development of Radioisotopes and Radiopharmaceuticals (CDRR) through non-commercial arrangement. The near-future strategic research programs to response to dynamic public demand are also discussed. The status of research cooperation with JAERI (Japan) is also reported. (author)

  17. An electro-amalgamation approach to avail 175Yb suitable for radiopharmaceutical applications

    Over the years, there has been considerable interest in identifying and using potential radionuclides for the development of various kinds of therapeutic radiopharmaceuticals.175 Yb (Eβ(max) = 480 keV (80%); Eγ = 113 keV (1.9%), 282 keV (3.1%), 396 keV (6.5%); T1/2 = 4.2 d) has been identified as one such potential radionuclide. 175Yb with adequately high specific activity for radiotherapeutic applications can be produced by using natural ytterbium oxide target employing the direct neutron capture route. However, one major impediment of using 175Yb produced following this route for the preparation of therapeutic radiopharmaceuticals is the presence 169Yb and 177Lu in the processed 175YbCl3 as the radionuclidic impurities. The presence of 169Yb in 175Yb is not expected to cause any serious problem in the radiotherapeutic applications. On the contrary, it may be useful in extended studies of the pharmacological characteristics of the 175Yb-labelled radiopharmaceuticals in biological systems and carrying out dosimetric evaluation of the administered radiopharmaceuticals. However, the presence of 177Lu, another potential therapeutic radionuclide, may be a cause of concern, as it has a different β- energy spectrum. Therefore, for wider acceptability of 175Yb as a potential radionuclide for targeted therapy, there is a need for the development of a method that can remove 177Lu from 175Yb. Herein, we describe the development of an electrochemical approach based on the selective reduction of Yb3+ to the divalent state and its preferential transfer on to a mercury cathode under the conditions of controlled applied potential. The suitability of 175Yb for the preparation of radiopharmaceuticals has been evaluated

  18. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents. PMID:27496068

  19. Development and clinical application of the radiopharmaceutical dried-kit of ciprofloxacin

    Nowadays, the 99mTc-ciprofloxacin radiopharmaceutical is available in the form of liquid-kit, which is separately packed with its radionuclide. The radiopharmaceuticals in that form has low stability. In order to fulfill the necessity of radiopharmaceutical for the diagnosis of infection, the modification of the preparation radiopharmaceutical dried-kit of ciprofloxacin using a commercial ciprofloxacin infuse solution by lyophilization method has been carried out. Ciprofloxacin dried-kit consists of 2 mg of ciprofloxacin lactate in the vial A and 2 mg of stannous tartrate in the vial B. The preparation of 99mTc-ciprofloxacin was performed by adding 99mTc radionuclide into the vial A dissolved in sterile water for injection, followed by addition of Sn-tartrate solution from the vial B at the optimum condition of labeling. The radiochemical purity of 99mTc-ciprofloxacin was analyzed by chromatographic method using ITLC-SG as a stationary phase and acetone as a mobile phase. In vitro determination of the biological activity and uptake of 99mTc-ciprofloxacin were performed to microorganism. Meanwhile, the sterility, toxicity and clinical evaluation were also observed. The labelling result of ciprofloxacin dried-kit with 99mTc radionuclide indicated that radiochemical purity of 99mTc-ciprofloxacin was 96.39 ± 2.01 %. The determination of biological activity to S. aureus and E. coli showed that after labelling the bactericide activity was not change i.e. 83.06 ± 10.95 % and 80.26 ± 8.58 % for S. aureus and E. coli respectively, whereas the maximum uptake were occurred after one hour incubation. Clinical evaluation of 99mTc-ciprofloxacin to liver and bone marrow abscess patients showed the radioactivity accumulation around those areas. Clinical application of 99mTc-ciprofloxacin with tomography technique using gamma camera showed that this radiopharmaceutical could be used for infection imaging. (author)

  20. Understanding radioxenon isotopical ratios originating from radiopharmaceutical facilities

    Saey, P. R. J.; Ringbom, A.; Bowyer, T. W.; Becker, A.; de Geer, L.-E.; Nikkinen, M.; Payne, R. F.

    2009-04-01

    It was recently shown that radiopharmaceutical facilities (RPF) are major contributors to the general background of 133Xe and other xenon isotopes both in the northern and southern hemisphere. To distinguish a nuclear explosion signal from releases from civil nuclear facilities, not only the activity concentrations but also the ratios of the four different CTBT relevant radioxenon isotopes (131mXe, 133mXe, 133Xe and 135Xe) have to be well understood. First measurements taken recently in and around two of the world's largest RPF's: NTP at Pelindaba, South Africa and IRE at Fleurus, Belgium have been presented. At both sites, also stack samples were taken in close cooperation with the facility operators. The radioxenon in Belgium could be classified in four classes: the normal European background (133Xe activity between 0 - 5 mBq/m3) on one hand and then the samples where all four isotopes were detected with 133mXe/131mXe > 1. In northern South Africa the Pelindaba RPF is in practice the sole source of radioxenon. It generated a background of 133Xe at the measurement site some 230 km to the west of the RPF of 0 - 5 mBq/m3. In the cases where the air from the Pelindaba facility reached the measurement site directly and in a short time period, the 133Xe was higher, also 135Xe was present and in some samples 133mXe as well. The ratios of the activity concentrations of 135Xe/133Xe vs. 133mXe/131mXe (Multiple Isotope Ratio Plot - MIRC) have been analysed. For both facilities, the possible theoretical ratio's for different scenarios were calculated with the information available and compared with the measurements. It was found that there is an excess of 131mXe present in the European samples compared to theoretical calculations. A similar excess has also been seen in samples measured in northern America. In South Africa, neither the environmental samples nor the stack ones contained 131mXe at measurable levels. This can probably be explained by different processes and

  1. Basic requirements of quality control of PET radiopharmaceuticals

    Background/Aim: PET radiopharmaceutical (RPs) require efficient, simple, and well established quality control (QC) procedures due to short half lives of radionuclides (15O: 120 sec; 13N: 10 min, 11C: 20 min, and 18F: 110 min) used in their synthesis. Although QC procedures have been recommended by FDA, these are far from complete and quite often difficult to perform routinely due to limited time, resources, and lack of expertise. We have established basic guidelines of radiation safety and QC for the production of 18F-dG and 18F-DOPA for clinical applications (Sharma et al 2006). This report is to share basic knowledge of standard operating procedures (SOPs) and advanced procedures with well established and developing labs. It is expected that our experience will be beneficial and adopted for the successful and economical maintenance of PET-RPs labs. Materials and Methods: SOPs were developed for checking temperature, pH, ionic concentrations, sterility, apyrogenicity, radiochemical purity, radionuclidic purity, and chemical purity. Mass spectroscopic procedure was developed for QC of PET-RPs with a special emphasis to 2-fluoro, 2-deoxy, D-glucose (18FdG) as it is used extensively in clinical diagnosis.For compliance testing, NMR (1H, 13C, 19F) and IR spectroscopic analyses were performed to check stability and shelf life of 18FdG and mannose triflate. To determine molecular weight, purity, reproducibility, and shelf life, Brukor-BioToff Mass spectrometer was used. Inductively coupled plasma mass spectroscopic (ICP-MS) and graphite furnace atomic mass spectroscopic (GF-AAS) analyses were performed to estimate metal ion impurities of cyclotron targetry. Results: We developed a simple, innovative, economical, and less time consuming mass spectroscopic procedure to determine chemical purity of PET-RPs. Overlay mass spectrograms of 37 production runs illustrating accuracy, sensitivity, reliability, and reproducibility are presented in Fig. 1. The radioHPLC and mass

  2. Preparation and evaluation of radiopharmaceuticals for infection imaging

    Aim: In this study Tc-99m labeled ubiquicidin peptide (UBI), DTPA-bisBiotin and ciprofloxacin were prepared and compared as their biodistribution and ability to detect and differentiate infection from a sterile inflammatory process in rats. Material and Methods: Human antimicrobial peptide, UBI 29-41, (Leiden University Medical Center, The Netherlands), was dissolved in 1 M sodium acetate buffer pH 5.2 (1 mg/200μL). For Tc-99m labeling 10 μL was added to a vial containing 3 μL of a fresh 1 mg/mL solution of stannous chloride in 10 mM HCl. To this was added 4 μL of a solution of 1.0 mg of NaBH4 per mL of 0.1 M NaOH, followed by 99mTc-pertechnetate in a volume of 100-1000 μL, obtaining a final pH between 8 and 9. DTPA-bisBiotin (Sigma),1mg, was dissolved in 100 μL of 1 M sodium acetate buffer pH 6. For labeling 50 μL was added to a vial containing 99mTc-pertechnetate in a volume of 10-20 μL. To this was added 2 μL of a fresh 1 mg/mL solution of stannous chloride in 10 mM HCl (final pH=6.0). Ciprofloxacin (Bayer), 10 mg, were dissolved in 5 mL of 0.9 % NaCl solution. Formamidine sulphonic acid, 10 mg, were dissolved in 6.25 mL of saline. From each solution 0.5 mL were withdrawn, mixed, and the pH adjusted to 8 with 0.5 M NaOH. Thereafter 0.5 mL of 99mTc-pertechnetate was added. The reaction mixture was heated at 920C during 10 min. The final pH was 7.0. Sixty six Wistar rats with bacteria induced infection (Staphylococcus aureus)/inflammation (Heat killed Klebsiella pneumoniae), were used to study the biodistribution of radiopharmaceuticals. Results: The radioactivity recovery for 99mTc-UBI was 98 ± 3 % determined by reverse phase HPLC and radiochemical purity 96 ± 2 % determined by SepPak cartridge. Considering that into UBI structure five of the thirteen total amino acids are Arginine (R) (which represents free -NH2 groups) and three of them almost beside Lysine (K), a possible molecular structure for 99mTc-UBI was calculated and simulated by Cerius2

  3. Harvard-MIT research program in short-lived radiopharmaceuticals. Progress report, March 1, 1983-February 29, 1984

    This report describes research efforts towards the achievement of a clearer understanding of the solution chemistry of technetium in order to facilitate the design of future clinical agents labeled with Tc-99m, the development of new receptor binding radiopharmaceuticals for the in vivo assessment of insulin receptors and for imaging the adrenal medulla and the brain, the examination of the utility of monoclonal antibodies and liposomes in the design of radiopharmaceuticals for diagnosis and therapy, and the synthesis of short-lived positron-emitting radiopharmaceuticals for transverse imaging of regional physiological processes

  4. World Radiopharmaceutical Therapy Council: A report on the 5th International Radiopharmaceutical Therapy Colloquium and the Final Planning Meeting of the World Radiopharmaceutical Therapy Council held at Santiago, Chile, 29 September, 2002

    Full text: The 5th International Radiopharmaceutical Therapy Colloquium was held on 29th October 2002 as a pre-congress meeting of the World Federation of Nuclear Medicine and Biology Congress in Santiago, Chile. Work-in-Progress research papers were presented by leaders in the field of therapeutic nuclear oncology. Speakers gave untitled presentations without abstracts and reported data from studies performed only days or weeks before the meeting. Such cutting edge research presentations stimulated lively discussion which also addressed the problems encountered and ways in which they may be circumvented. Radioimmunotherapy of haematological malignancy was discussed by Greg Wiseman of the Mayo Clinic, and Thomas Behr of the University of Marburg. Radiopeptide therapy of neuroendocrine tumours was presented by Larry Kvols from the University of Florida, and locoregional therapy of glioma was presented by John Buscombe of the Royal Free Hospital, London. All speakers reported encouraging clinical results with objective tumour responses, increased survival and improved quality of life, which encourages wider clinical application of these novel radiopharmaceutical therapies. The Round Table Discussion on clinical applications of Rhenium-188 radiopharmaceuticals was chaired by Russ Knapp from Oak Ridge National Laboratory and Hans Biersack of the University of Bonn. Following an outline of current developments by Russ Knapp preliminary results of clinical trials were presented for discussion. Hans Biersack, Javier Gaudiano from Montevideo and Achim Kropp from Dresden reported effective palliation of painful skeletal metastases with 188Re-HEDP. Ajit Padhy gave an update of the IAEA multicentre trial of intrahepatic arterial 188Re-Lipiodol therapy of hepatocellular carcinoma and Harvey Turner reported preliminary results in hepatoma patients using an alternative kit formulation of 188Re-Lipiodol in Fremantle. Early experience with Rhenium 188 in the prevention of re

  5. AERONET Version 3 processing

    Holben, B. N.; Slutsker, I.; Giles, D. M.; Eck, T. F.; Smirnov, A.; Sinyuk, A.; Schafer, J.; Rodriguez, J.

    2014-12-01

    The Aerosol Robotic Network (AERONET) database has evolved in measurement accuracy, data quality products, availability to the scientific community over the course of 21 years with the support of NASA, PHOTONS and all federated partners. This evolution is periodically manifested as a new data version release by carefully reprocessing the entire database with the most current algorithms that fundamentally change the database and ultimately the data products used by the community. The newest processing, Version 3, will be released in 2015 after the entire database is reprocessed and real-time data processing becomes operational. All V 3 algorithms have been developed, individually vetted and represent four main categories: aerosol optical depth (AOD) processing, inversion processing, database management and new products. The primary trigger for release of V 3 lies with cloud screening of the direct sun observations and computation of AOD that will fundamentally change all data available for analysis and all subsequent retrieval products. This presentation will illustrate the innovative approach used for cloud screening and assesses the elements of V3 AOD relative to the current version. We will also present the advances in the inversion product processing with emphasis on the random and systematic uncertainty estimates. This processing will be applied to the new hybrid measurement scenario intended to provide inversion retrievals for all solar zenith angles. We will introduce automatic quality assurance criteria that will allow near real time quality assured aerosol products necessary for real time satellite and model validation and assimilation. Last we will introduce the new management structure that will improve access to the data database. The current version 2 will be supported for at least two years after the initial release of V3 to maintain continuity for on going investigations.

  6. MAD Version 9

    Iselin, F Christoph; Pancin, J; Adelmann, A

    2000-01-01

    The program MAD is widely used for accelerator design and beam dynamics studies. For many years, its input language has been the nearest thing to a world-wide standard for describing accelerator structures. The new Version 9 is a complete rewrite using a systematic object-oriented methodology based on the CLASSIC classes [2] for accelerator physics. It provides many improvements over the previous MAD Version 8. These include: (i) support for multiple beam-lines simultaneously, facilitating, for example, matching constraints that couple the two rings of a two-ring collider, (ii) much improved Lie-algebraic map calculations, (iii) a uniform method and format for exchanging many kinds of structured data with other programs, (iv) an improved and more consistent input language. In addition, we report on a parallel 3D Poisson field solver for space charge calculations in high intensity particle beams. Applied to the PSI injector cyclotron, this shows the general nature of MAD Version 9 as a state-of- the-art proble...

  7. Open source version control software

    Seppänen, V

    2015-01-01

    The environment around open source version control software is very opinionated and therefore it is hard to find unbiased comparison between different open source version control software. This Bachelor’s thesis provides background and covers the basics of version control systems. Thesis also categorizes and differentiates the main types of version control systems, by investigating the way they handle repositories and by categorizing them to centralized and distributed. Finally, this thesis p...

  8. Preliminary study fo the interference of proteic compounds of radiopharmaceuticals in the test of lisadode amebocitos de limulus (LAL)

    Aldana, C

    1997-01-01

    In this thesis the objective was evaluate the interference of proteic compounds of the radiopharmaceuticals in the test LAL (lisado of amebocitos de limulus) for this, macroagregates of albumina (MAA) was used with metilendifosfonato (MDP) as control that is the radiopharmaceutical more used in the nuclear medicine centers of the country. Initially preliminary test were carried out to assess if some of two radiopharmaceuticals would cause interference with LAL test, after the test was validated and finally routine tests were made. With the preliminary assays was concluded that proteic compounds did not cause interference (albumina with a concentration of 2 md/dl) with the MAA. However with the MDP cause interference with LAL test. The interference was eliminated with a dilution of 1:8 of the sample. Was concluded that the success of LAL test depends on conditions such as temperature, pH, constant incubation (no minimum variations) and that is a good test for quality control of the radiopharmaceuticals.

  9. Preliminary study fo the interference of proteic compounds of radiopharmaceuticals in the test of lisadode amebocitos de limulus (LAL)

    In this thesis the objective was evaluate the interference of proteic compounds of the radiopharmaceuticals in the test LAL (lisado of amebocitos de limulus) for this, macroagregates of albumina (MAA) was used with metilendifosfonato (MDP) as control that is the radiopharmaceutical more used in the nuclear medicine centers of the country. Initially preliminary test were carried out to assess if some of two radiopharmaceuticals would cause interference with LAL test, after the test was validated and finally routine tests were made. With the preliminary assays was concluded that proteic compounds did not cause interference (albumina with a concentration of 2 md/dl) with the MAA. However with the MDP cause interference with LAL test. The interference was eliminated with a dilution of 1:8 of the sample. Was concluded that the success of LAL test depends on conditions such as temperature, pH, constant incubation (no minimum variations) and that is a good test for quality control of the radiopharmaceuticals

  10. Vincristine: effect on the biodistribution of 99mTc-Phytic radiopharmaceutical in Balb/cJ mice

    The biodistribution of pharmacokinetics of radiopharmaceuticals may be altered by drugs, disease states, surgical procedures and irradiation. If unknown, such factors may lead to misdiagnosis. Thus, it is necessary to investigate the effect of therapeutic drugs in the biodistribution of 99m Tc-radiopharmaceuticals in the body. Here, we have studied the effect of vincristine in the biological distribution of 99m Tc-Phytic, employed to hepatic scintigraphies. In our study vincristine has decreased the radiopharmaceutical uptake in: ovary, uterus, heart and kidney, has increased the radioactivity in pancreas, brain and bone, and did not modify the uptake of the radiopharmaceutical in: spleen, liver stomach, thymus, lungs and thyroid. Those results can be explained by different biological effects of vincristine in the various organs. (author)

  11. A self-control study of three radiopharmaceuticals for locating sentinel lymph node

    Objective: To compare the uptake of antimony colloid, sulfur colloids and DX in the parasternal lymph node of rabbits and to investigate which one is the most suitable for locating sentinel lymph node. Methods: Six rabbits were used in this auto-control study. Radio labeled sulfur colloids, antimony colloid or DX was injected subcutaneously at both side of the xiphoid process. For each rabbit, which pharmaceutical injected firstly and secondly was at random. At first, one of the three pharmaceuticals was used. After a certain period of time, radioactivity of the chest wall of the rabbits was detected. If the radioactivity was proven to be as low as background, another kind of radiopharmaceuticals was injected and the radioactivity was detected. Then after another period of time, the last radiopharmaceutical was injected if the radioactivity of the chest wall was proven to be low enough. The sites of injection were marked. Whole body scan was performed at different time after injection. Radioactivity of the parasternal lymph node and the injected sites was detected with gamma probe. Uptake-time curves were drawn for the three radiopharmaceuticals. The relationship between size of particle and lymphatic uptake rate was studied. Results: At 4 hours after injection, the percent uptake of DX, sulfur colloids and antimony colloid was 10.41% +/- 0.92%, 3.16% +/- 0.30% and 8.06% +/- 0.50, respectively. The difference among the uptake rate of the three radiopharmaceuticals in the parasternal lymph node was statistically significant (p<0.05). The radiopharmaceutical that is the smallest in diameter in this research was DX, which moved quickly along the lymphatic chain. The ratio of radioactivity of the first lymph node to other lymph node along the lymphatic chain was not high enough and the first lymph node can not be easily identified by gamma probe. Sulfur colloid was the largest in diameter. It was trapped by the first lymph node along the lymphatic chain after being

  12. Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals

    Introduction: The chick embryo is an emerging in vivo model in several areas of pre-clinical research including radiopharmaceutical sciences. Herein, it was evaluated as a potential test system for assessing the biodistribution and in vivo stability of radiopharmaceuticals. For this purpose, a number of radiopharmaceuticals labeled with 18F, 125I, 99mTc, and 177Lu were investigated in the chick embryo and compared with the data obtained in mice. Methods: Chick embryos were cultivated ex ovo for 17–19 days before application of the radiopharmaceutical directly into the peritoneum or intravenously using a vein of the chorioallantoic membrane (CAM). At a defined time point after application of radioactivity, the embryos were euthanized by shock-freezing using liquid nitrogen. Afterwards they were separated from residual egg components for post mortem imaging purposes using positron emission tomography (PET) or single photon emission computed tomography (SPECT). Results: SPECT images revealed uptake of [99mTc]pertechnetate and [125I]iodide in the thyroid of chick embryos and mice, whereas [177Lu]lutetium, [18F]fluoride and [99mTc]-methylene diphosphonate ([99mTc]-MDP) were accumulated in the bones. [99mTc]-dimercaptosuccinic acid (99mTc-DMSA) and the somatostatin analog [177Lu]-DOTATOC, as well as the folic acid derivative [177Lu]-DOTA-folate showed accumulation in the renal tissue whereas [99mTc]-mebrofenin accumulated in the gall bladder and intestine of both species. In vivo dehalogenation of [18F]fallypride and of the folic acid derivative [125I]iodo-tyrosine-folate was observed in both species. In contrast, the 3′-aza-2′-[18F]fluorofolic acid ([18F]-AzaFol) was stable in the chick embryo as well as in the mouse. Conclusions: Our results revealed the same tissue distribution profile and in vivo stability of radiopharmaceuticals in the chick embryo and the mouse. This observation is promising with regard to a potential use of the chick embryo as an inexpensive

  13. The Radiopharmaceuticals Production and Research Centre established by the Heavy Ion Laboratory of the University of Warsaw

    Choiński J.; Jastrzębskia J.; Kilian K.; Mazur I.; Napiorkowski P.J.; Pękal A.; Szczepaniak D.

    2014-01-01

    The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- ). Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centr...

  14. Effect of vincristine on biodistribution of sodium pertechnetate and 99 m Tc-phytate radiopharmaceuticals in mice balb/c

    Vincristine is a drug used in chemotherapy for cancer treatment. The radiopharmaceuticals biodistribution or pharmacokinetics can be modify by drugs effect, diseases, surgery and radiotherapy. The absence of knowledge of these factors may result in an unexpected behavior of the radiopharmaceuticals. In this work was studied the effect of vincristine on biodistribution of pertechnetate used for thyroid and brain scintigraphy and 99 mTc-phytate used for hepatic scintigraphy. 5 refs., 5 tabs

  15. Preparações radiofarmacêuticas e suas aplicações Radiopharmaceuticals and applications

    Rita Oliveira

    2006-06-01

    ármacos em uso clínico corresponde a agentes de perfusão. Atualmente, o esforço de investigação na área da química radiofarmacêutica centra-se no desenvolvimento de radiofármacos específicos que possam fornecer informação, ao nível molecular, relativa às alterações bioquímicas associadas às diferentes patologias.Radiopharmaceuticals are substances without pharmacological activity that are used in Nuclear Medicine for diagnosis and therapy for several diseases. Diagnosis radiopharmaceuticals generally emit gamma radiation or positrons (beta+, because their decay originates penetrating electromagnetic radiation that can cross the tissues and be externally detected. Therapeutic radiopharmaceuticals must include in their composition ionized particles emission nucleus (a, b- or Auger electrons, since their action is based in selective tissue destruction. There are two main methods for image acquisition: SPECT (Single Photon Emission Computerized Tomography that uses g emission radionuclides (99mTc, 123I, 67Ga, 201Tl and PET (Positron Emission Tomography that uses positron emission radionuclides like 11C, 13N, 15O, 18F. Radiopharmaceuticals can be classified into perfusion radiopharmaceuticals (first generation or specific radiopharmaceuticals (second generation. Perfusion radiopharmaceuticals are transported in the blood e reach the target organ in the direct proportion of the blood stream. Specific radiopharmaceuticals contain a biologically active molecule that binds to cellular receptors that must remain biospecific after binding to the radiopharmaceutical. For this type of radiopharmaceuticals, tissue or organ uptake is determined by the biomolecule capacity of recognizing receptors in those biological structures. Radiopharmaceuticals are produced ready to use, in cold kits or in autologal preparations. According to the preparation type there is a different quality control procedure. Most of the radiopharmaceuticals used nowadays are of the perfusion type

  16. Nuflood, Version 1.x

    2016-07-29

    NUFLOOD Version 1.x is a surface-water hydrodynamic package designed for the simulation of overland flow of fluids. It consists of various routines to address a wide range of applications (e.g., rainfall-runoff, tsunami, storm surge) and real time, interactive visualization tools. NUFLOOD has been designed for general-purpose computers and workstations containing multi-core processors and/or graphics processing units. The software is easy to use and extensible, constructed in mind for instructors, students, and practicing engineers. NUFLOOD is intended to assist the water resource community in planning against water-related natural disasters.

  17. PVWatts Version 5 Manual

    Dobos, A. P.

    2014-09-01

    The NREL PVWatts calculator is a web application developed by the National Renewable Energy Laboratory (NREL) that estimates the electricity production of a grid-connected photovoltaic system based on a few simple inputs. PVWatts combines a number of sub-models to predict overall system performance, and makes includes several built-in parameters that are hidden from the user. This technical reference describes the sub-models, documents assumptions and hidden parameters, and explains the sequence of calculations that yield the final system performance estimate. This reference is applicable to the significantly revised version of PVWatts released by NREL in 2014.

  18. TOGAF version 9

    Group, The Open

    2010-01-01

    This is the official Open Group Pocket Guide for TOGAF Version 9 Enterprise Edition. This pocket guide is published by Van Haren Publishing on behalf of The Open Group.TOGAF, The Open Group Architectural Framework is a fast growing, worldwide accepted standard that can help organisations build their own Enterprise Architecture in a standardised way. This book explains why the in?s and out?s of TOGAF in a concise manner.This book explains how TOGAF can help to make an Enterprise Architecture. Enterprise Architecture is an approach that can help management to understand this growing complexity.

  19. Eichrom's ABEC trademark resins: Alkaline radioactive waste treatment, radiopharmaceutical, and potential hydrometallurgical applications

    Eichrom's ABEC trademark resins selectivity extract certain anions from high ionic strength acidic, neutral, or strongly alkaline media, and solute stripping can be accomplished by eluting with water. ABEC resins are stable to pH extreme and radiolysis and operate in high ionic strength and/or alkaline solutions where anion-exchange is often ineffective. Potential applications of the ABEC materials include heavy metal and ReO4- separations in hydrometallurgy and purification of perrhenate iodide, and iodate in radiopharmaceutical production. Separation of 99mTcO4- from its 99MoO42- parent and stripping with water or physiological saline solution have been demonstrated for radiopharmaceutical applications. Removal of 99TcO4- and 129I- from alkaline tank wastes has also been successfully demonstrated. The authors will discuss the scale-up studies, process-scale testing, and market development of this new extraction material

  20. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1978-October 31, 1979

    Although the germanium-gallium generator is probably the only source of positron-emitting radionuclides that would enable the wide application of positron tomography, the generator system in use suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, and EDTA forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than gallium-68 EDTA it is necessary to break the stable EDTA complex and remove all the EDTA. A new generator system using a solvent extraction system which will produce gallium-68 8-hydroxyquinoline, a weak chelate has been developed. Using this agent, several gallium-68 radiopharmaceuticals have been synthesized and tested in vitro and in vivo. Attempts have been made using polarographic and chromatographic techniques to investigate the stability of gallium-68 complexes with a series of cryptates

  1. Radiological impact from the transport of radiopharmaceuticals of the IPEN/CNEN-SP

    When a package is shipped, people who work, live or travel in the route used for transportation of radioactive materials are irradiated, as well as those who are inside vehicles that travel in the same or opposite directions. Therefore, the proposed work has as main objective to estimate the radiological impact of the transportation of radiopharmaceuticals of IPEN/CNEN-SP to some predefined destinations. The doses in individuals who are in the public streets and in vehicles that travel close to the means of transportation, along the route traveled by packages, during the transport of radiopharmaceuticals were estimated. The doses were also estimated for drivers, from both the operation of driving the vehicle, and the loading and unloading of packages, because these tasks are performed by the drivers. (author)

  2. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  3. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1980 - December 31, 1983

    The germanium-68/gallium-68 generator system is an ideal generator system for carrying out studies using positron-emission tomography in institutions without an in-house cyclotron. We have compared two new generator systems with a commercially available system and conclude that the preferred system is a stannous oxide column from which the gallium-68 is eluted using hydrochloric acid. We have attempted to prepare a series of lipophilic gallium radiopharmaceuticals for use in the measurement of cerebral and myocardial blood flow. As part of this study, we have attempted to define the ranges of lipophilicility and molecular weight necessary for an agent to be a suitable flow tracer. Our data suggest that, although gallium radiopharmaceuticals based on the enterobactin structure are stable in vivo, their molecular weights are too high for use as flow tracers. A series of salicylimines recently developed appear to have potential for use as gallium-68 flow tracers

  4. Specific activity determination and stability studies of therapeutic 131I-mIBG radiopharmaceutical

    Board of Radiation and Isotope Technology, India is a manufacturer and supplier of therapeutic doses of the 131I-meta-iodobenzylguanidine to various nuclear medicine centers in India. The therapeutic dosage of radiopharmaceutical involves a single variable dose of >3.7 GBq activity. Since the radiopharmaceutical produced is mainly by isotope exchange, which yields a low specific activity product, the determination of its accurate mass is a critical parameter for its safe administration in patients. In view of this, a suitable high performance liquid chromatography (HPLC) method has been developed for the determination of specific activity with high precision. Also, quantification of stability in terms of the % radiochemical purity of the formulation >370 MBq/mL supplied, under different storage conditions over time was carried out using the developed HPLC method. (author)

  5. Radiation dose calculations for orally administered radio-pharmaceuticals in upper gastrointestinal disease

    Radiation burden estimates for upper gastrointestinal function studies employing the following orally administered radiopharmaceuticals are reported. Technetium 99m sulfur colloid (Tc-99m-SC) in water, Indium-111-DTPA in water, Tc-99m-DTPA in water, Indium-113m DTPA in water, Tc-99m Ovalbumin, Tc-99m sulfur colloid in a cooked egg, Tc-99m sulfur colloid in vivo labeled chicken liver, and Indium-111 colloid in vivo labeled chicken liver. Orally administered radiopharmaceuticals for upper gastrointestinal studies afford clinician and investigator valuable clinical and physiologic information not previously obtainable using other techniques. The radiation burden to the patient from single or sequential studies is acceptable in comparison to fluoroscopy which results in approximately 5000 millirem per minute of exposure. The variety of preparations listed above should make these types of studies available in any routinely equipped nuclear medicine radiopharmacy laboratory

  6. Forschungszentrum Rossendorf, Institute of Bioinorganic and Radiopharmaceutical Chemistry. Annual report 1995

    Research at the Institute of Bioinorganic and Radiopharmaceutical Chemistry of the Research Center Rossendorf is focused on radiotracers as molecular probes for diagnosis of disease. The research effort has two main components: -Positron emission tomography (PET) - technetium chemistry and radiopharmacology. The research activities of the Institute have been performed in three administratively classified groups. A PET tracer group is engaged in the chemistry and radiopharmacy of 11C and 18F compounds and in the setup of the PET center. A SPECT tracer group deals with the design, synthesis and chemical characterization of metal coordination compounds, primarily rhenium and technetium complexes. A biochemical group is working on SPECT and PET-relevant biochemical and biological projects. This includes the characterization and assessment of new compounds developed in the two synthetically oriented groups. The annual report presented here covers the research activities of the Institute of Bioinorganic and Radiopharmaceutical Chemistry in 1995. (orig.)

  7. Solution for backfitting of a controlled atmosphere area in radiopharmaceuticals unit: the mobile unit of decontamination

    The laboratory of radiopharmaceuticals preparation is a controlled area, defined by good practices of preparation. In order to answer to this regulatory requirement, the environment follow-up is made regularly by the hygiene service of the Grenoble University hospital center (C.H.U.). The results of the last sampling turned out to be wrong. Our objective are to remedy this air contamination and to improve the particulate air quality. A mobile unit of air cleaning allowed to be in accordance with the law at the air cleanliness level for the area of radiopharmaceuticals preparation at the Grenoble C.H.U.. It allows to answer to exigence of good practices of preparation face to the controlled atmosphere areas, in a rapid way, efficient way and cheap way, especially before the reorganization of radiopharmacy place. (N.C.)

  8. Dosimetry of renal radiopharmaceuticals: the importance of bladder radioactivity and a simple aid for its estimation

    The contribution from radioactivity in bladder contents to dose commitments to the embryo, ovaries, red marrow, kidney, bladder wall and total body has been estimated for various renal radiopharmaceuticals, assuming a bladder-voiding period of 3.5 h. For hippuran and GFR agents this contribution is 70-97% of the embryo dose and 50-93% of the ovary dose. The embryo dose exceeds the ovary dose by a factor of two or more. For the radiopharmaceuticals with no significant kidney retention, the surface dose to the bladder wall is higher, by more than an order of magnitude, than doses to other organs and is largely responsible for the effective dose equivalent exceeding the estimated whole-body dose by factors of up to 25. Since the estimation of cumulated activity in bladder contents is necessary for bladder dosimetry, a nomogram based on a 3.5 h voiding period is presented as a convenient aid for this purpose. (author)

  9. Detection of sentinel lymphnode using radiopharmaceuticals methods, importance and safety handling

    Yokoyama, Kunihiko; Nakajima, Kenichi; Tonami, Norihisa; Tugawa, Koichiro; Noguchi, Masakuni [Kanazawa Univ. (Japan). Hospital

    2000-04-01

    In our district, there is no approved radiopharmaceutical appropriate for lymphoscintigraphy. Thus, we have attempted to evaluate the three radiopharmaceuticals such as {sup 99m}Tc-human serum albumin (HSA), {sup 99m}Tc-tin colloid (TC) and {sup 99m}Tc-phytate for this application. HSA demonstrated the sentinel LNs in 35 out 49 cases. However, it traveled so rapid that LNs might tend to be visualized more than the sentinel LN. TC was so big in size that it could only visualize the sentinel LNs in 18 out of 33 cases. Although the number of patients who received phytate is limited, it seemed to detect sentinel LNs better that the other 2 compounds. (author)

  10. Quantitative studies in radiopharmaceutical science. Progress report, January 1-December 31, 1985

    This program, during the past 30 years, has developed with the constant awareness of the close interrelationships and interdependence between clinical needs, radiopharmaceutical and instrument developments, and clinical feasibility studies. This is a year of transition for this contract with two of the responsible investigators, Katherine Lathrop and Paul Harper, reaching the age of mandatory retirement. This report focuses on the completion and write-up of current research projects by Dr. Harper and Mrs. Lathrop. 4 refs

  11. The Growing Impact of Bioorthogonal Click Chemistry on the Development of Radiopharmaceuticals

    Zeng, Dexing; Zeglis, Brian M; Lewis, Jason S.; Anderson, Carolyn J.

    2013-01-01

    Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This ...

  12. Radioactivity resistance evaluation of polymeric materials for application in radiopharmaceutical production at microscale

    Zacheo, A.; Arima, Valentina; Pascali, Giancarlo; Salvadori, Piero; Zizzari, A; Perrone, E; De Marco, L; Gigli, G.; Rinaldi, Ross

    2011-01-01

    Abstract Microfluidic technologies are gaining increasing importance due to their capability of manipulating fluids at the microscale that should allow to synthesize many products with surprisingly high yields and short reaction times. In the lab-on-chip field researchers have developed microfluidic apparatuses to provide special equipments for producing positron emission tomography (PET) radiopharmaceuticals in a quicker, safer, and more reliable way compared to traditional vessel-based appr...

  13. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    Vadim Bernard-Gauthier; Carmen Wängler; Esther Schirrmacher; Alexey Kostikov; Klaus Jurkschat; Bjoern Wängler; Ralf Schirrmacher

    2014-01-01

    Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET). These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F) to either an aliphatic or aromatic carbon atom. One method in part...

  14. Options for shielding the hand during dispensing and administration of radiopharmaceuticals

    Hospital staff manipulating radiopharmaceuticals may receive significant radiation doses to their hands. A study of hand doses has been carried out in a large radionuclide dispensary and in nuclear medicine departments in the West of Scotland and the implications of different shielding options considered. Doses received for individual manipulation during many routine sessions have been measured with an electronic extremity dose monitor. Doses received from dispensing of radiopharmaceuticals in nuclear medicine were 4 mGy per 10 GBq handled, compared to 0.2 mGy per 10 GBq for radionuclide dispensary staff. There were a number of reasons for the large difference, with one of the most important being the speed with which the manipulations were performed. The actions performed in nuclear medicine consist of dispensing into a syringe and injection. Withdrawal of radiopharmaceuticals made up the higher dose component 5 to 500 μSv per procedure as a siring shield was not used for this part of the procedure. Doses received from individual injections for which syringe shields were used varied from 1.5 to 300 μSv depending on the degree of difficulty experienced during the injection. The study has shown the effectiveness of using local shielding in dose reduction. Tungsten vial shields limit the radiation dose and are useful for handling large activities during radiopharmaceutical preparation. Syringe shields substantially reduce doses for individual manipulations and should be used for procedures in which accurate reading of the syringe scale is not required. This includes higher dose manipulations in the radionuclide dispensary and injections in nuclear medicine. (Author)

  15. The excretion of radiopharmaceuticals in human breast milk: additional data and dosimetry

    The amount of radioactivity excreted in breast milk following administration of 11 different radiopharmaceuticals, has been measured. This report summarises the data collected from 60 patients. An effective decay constant for the series of samples from each patient was calculated. In order to formulate reliable guidelines, we calculated the total activity theoretically excreted in milk until complete decay of the radionuclide. Of the various 99mTc compounds, pertechnetate clearly reaches the highest concentrations in breast milk. The wide variability of data from different patients who received the same radiopharmaceutical despite identical methods of sample collection and data processing confirms the impression gained from literature that transfer of radionuclides into milk varies greatly between individuals. We believe that for radiation protection purposes, a ''worst case'' approach is the most appropriate. With new data available and the revision of ICRP recommendations, the guidelines applicable when radiopharmaceuticals are administered to breast-feeding mothers are reviewed. The effective dose resulting from close contact between patient and infant was included in these calculations. Breast feeding need not be interrupted after administration of 99mTc-DISIDA, -sulphur colloid, -gluconate and -methoxyisobutylisonitrile (MIBI). However, after administration of 99mTc-MIBI, close contact should be restricted. 99mTc-pyrophosphate and -microspheres require interruption periods of several hours. High activities of 99mTc-pertechnetate may require interruption longer than 2 days. For pertechnetate and 99mTc-labelled red blood cells, interruption of breast feeding with measurement of activity in expressed milk samples is recommended. Breast feeding is contra-indicated after administration of 67Ga and 131I. General guidelines regarding breast feeding after administration of radiopharmaceuticals are summarised. (orig./MG)

  16. The preparation of organic radiopharmaceuticals and labelled compounds using short-lived cyclotron-produced radionuclides

    Accelerator-produced nuclides and radiopharmaceutical production are discussed with examples of pertinent methods of isotope production, methods of incorporation into organic molecules, and the general problems attandant on the production and use of these materials in this new and interdisciplinary effort. The literature is surveyed with stress being given to the use of 11C, 13N and 15O. 205 references are included. (author)

  17. Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals

    We propose the exploration of novel radionuclides with diagnostic or therapeutic properties from ISOLDE. Access to such unique isotopes will enable the fundamental research in radiopharmaceutical science towards superior treatment, e.g. in nuclear oncology. The systematic investigation of the biological response to the different characteristics of the decay radiation will be performed for a better understanding of therapeutic effects. The development of alternative diagnostic tools will be applied for the management and optimization of radionuclide therapy.

  18. Development new radiopharmaceutical based on 5-thio-d- glucose labeled technetium-99m

    Stasyuk, E. S.; Skuridin, V. S.; Ilina, E. A.; Rogov, A. S.; Nesterov, E. A.; Sadkin, V. L.; Larionova, L. A.; Varlamova, N. V.; Zelchan, R.

    2016-06-01

    The article considers the obtaining and possibility of using 5-thio-D-glucose labeled technetium-99m for the diagnosis of malignant tumors by single photon emission computed tomography. The analysis of the level of international developments of radiopharmaceuticals based on derivatives of glucose has been carried out. Also the article provides information on of using experimental batches of lyophilisate on the basis of 5-thio-D-glucose for preliminary biomedical testing on the mice.

  19. Physical-chemistry characteristic of 99mTc-human serum albumin (HSA)-nanospheres radiopharmaceutical

    Lymphoscintigraphy is one of diagnostic method which is conducted by injecting a colloidal radiopharmaceutical labeled technetium-99m which have ideally size of 100-200 nm in diameters by intradermal, subcutaneous or peritumoral route. The radiopharmaceutical movement in the lymphatic vessel can be detected from external side using gamma camera or a special probe for lymphoscintigraphy parallelly with surgery of tumor or cancer especially breast cancer. In the year of 2006 and 2007 have succeeded to be carried out designed and formulated of 99mTc-HSA-nanospheres is representing one of the nanocolloid radiopharmaceutical which is having the biodegradable and bioavailable characters. In the year of 2008, the study was continued to study of physical-chemistry characteristic of 99mTc-HSA-nanospheres, including radiochemical purity, pH, lipophilicity, plasma protein binding, electricity charge, stability after storage at certain temperature and in the plasmatic media. The results shows that 99mTc-HSA-nanospheres radiopharmaceutical have radiochemical purity of 92,1 ± 2,6%, pH = 6,5 - 7, its number of lipophilicity was 0,127 ± 0,03, plasma protein binding 89,6 ± 1,2% and neutral electricity charge. After 30 minutes, it was kept at room temperature, its radiochemical purity slow down became 71%, while if it was kept at temperature of 4°C (refrigerator) after one hour the radiochemical purity still more than 90%. In vitro plasmatic stability indicated that radiochemical purity was go down drastically, started from 30 minutes later, then one hour that was 61,8% and 55,9%, and at 2, 3 and until four hours storage this value did not change significantly that was 57,8%, 51,2%, 52% and after 24 hours became 8,2%. (author)

  20. labelling and quality control of some 99m Tc-radiopharmaceuticals of expected biological activity

    this thesis addresses the labelling and quality control of some 99mTc-radiopharmaceuticals which could be used for infection imaging. this study focuses on the labelling of sarafloxation, gatifloxation and cefepine with technetium-99m and biological evaluation of these labeled complexes and biodistribution in both normal and inflamed mice. the thesis is organized into two chapters: chapter I :labelling of some antibiotics chapter II :biological evaluation.

  1. Quantitative studies in radiopharmaceutical science. Progress report, April 1-August 31, 1986

    This report covers progress made during the first reporting period since the redirection of the project. In radiochemistry, achievements in fluorine-18 tracer studies including purification and reaction kinetics of 2-fluorodeoxyglucose and production of 6-fluoroDOPA. Radiopharmaceuticals have been prepared and tested for studies on CNS dopaminergic systems. By use of dynamic positron emission tomography the cerebral transport and metabolism of glucose continues to be studied. 6 figs

  2. Assessing the quality of 99mTc generators used for the preparation of radiopharmaceuticals

    Eluates were studied from radioisotope generators from 6 manufacturers. All were of chromatographic type containing 99Mo adsorbed on an aluminium oxide column. The following quality parameters were evaluated: technetium yield, radionuclide purity, radiochemical purity, clarity and color, acidity, aluminium content, and sterility. All generators yielded eluates meeting all requirements of the Czechoslovak State Standard and suitable for the preparation of radiopharmaceuticals. (M.D.). 3 tabs., 9 refs

  3. Mercaptoacetyltriglycine (MAG 3)-99mTc - a novel radiopharmaceutical for uropoietic system diagnosis

    Mercaptoacetyltriglycine (MAG 3) labelled with 99mTc is a novel prospective diagnostic agent for the uropoietic system which can replace injections of sodium iodohippurate labelled with 131I. Discussed are the procedure of labelling this novel radiopharmaceutical with 99mTc, evaluation of its quality by chromatographic methods, and bioavailability of MAG 3 in laboratory animals in comparison with that of injections of sodium iodohippurate labelled with 131I. (author). 8 figs., 7 refs

  4. Innovative complexation strategies for the introduction of short-lived PET isotopes into radiopharmaceuticals

    A number of TRAP (Triazacyclononane-triphosphinate) chelators were evaluated for labelling with Gallium-68. Based on the obtained data, a novel bifunctional chelator NOPO was designed, synthesised and employed for preparation of Ga-68 radiopharmaceuticals. Several 68Ga-labelled NOPO peptidic conjugates showed promising results in preclinical positron emission tomography (PET) imaging studies using the mice models. Moreover, NOPO was found also suitable for labelling with Copper-64.

  5. URGENCES NOUVELLE VERSION

    Medical Service

    2002-01-01

    The table of emergency numbers that appeared in Bulletin 10/2002 is out of date. The updated version provided by the Medical Service appears on the following page. Please disregard the previous version. URGENT NEED OF A DOCTOR GENEVAPATIENT NOT FIT TO BE MOVED: Call your family doctor Or SOS MEDECINS (24H/24H) 748 49 50 Or ASSOC. OF GENEVA DOCTORS (7H-23H) 322 20 20 PATIENT CAN BE MOVED: HOPITAL CANTONAL 24 Micheli du Crest 372 33 11 382 33 11 CHILDREN'S HOSPITAL 6 rue Willy Donzé 382 68 18 382 45 55 MATERNITY 24 Micheli du Crest 382 68 16 382 33 11 OPHTALMOLOGY 22 Alcide Jentzer 382 84 00 HOPITAL DE LA TOUR Meyrin 719 61 11 CENTRE MEDICAL DE MEYRIN Champs Fréchets 719 74 00 URGENCES : FIRE BRIGADE 118 FIRE BRIGADE CERN 767 44 44 BESOIN URGENT D'AMBULANCE (GENEVE ET VAUD) : 144 POLICE 117 ANTI-POISON CENTRE 24H/24H 01 251 51 510 EUROPEAN EMERGENCY CALL: 112 FRANCE PATIENT NOT FIT TO BE MOVED: call your family doctor PATIENT CAN BE MOVED: ST. JULIE...

  6. Report of a Technical Meeting on ''Alpha emitting radionuclides and radiopharmaceuticals for therapy''

    Considering the high potential of α-emitters for future development of radionuclide therapy, the International Atomic Energy Agency (IAEA) organized a Technical Meeting on ‘Alpha Emitting Radionuclides and Radiopharmaceuticals for Therapy’, from June 24 to 28, 2013, at IAEA Headquarters in Vienna with the purpose of gathering eminent Experts in the field and discuss with them the status and future perspectives of the field. Sixteen Experts and two External Observers from ten different countries, and four IAEA Technical Officers attended this meeting. Outstanding lectures have been presented covering all relevant aspects of α-therapy, which were followed by extensive discussions and analysis. Selected arguments encompassed production methods and availability of alpha-emitting radionuclides, labelling chemistry of alpha-emittting radioelements, design and development of target-specific radiopharmaceuticals, physical principles of alpha-particle dosimetry and advanced dosimetric models, biological effects of alpha radiation at the cellular level, on-going preclinical and clinical studies with new radiopharmaceuticals, results of clinical trials on the use of radium-223 chloride solutions for the treatment of metastatic bone cancer. The broad scientific background of invited components of the Experts’ panel conferred a strong interdisciplinary trait to the overall discussion and stimulated a critical analysis of this emerging unexplored field. Results of this comprehensive overview on alpha therapy, including recommendations to the Agency on suitable initiatives that may help to promote and spread the knowledge to Members States on this emerging therapeutic modality, are summarized in the present Report

  7. Report of the consultants' meeting on comparative laboratory evaluation of therapeutic radionuclides and radiopharmaceuticals

    Therapeutic radiopharmaceuticals consist of two components - the radionuclide and the biological carrier. With regard to the radionuclide, an advantage of targeted radiotherapy is that there are a wide variety of radionuclides with different physical half-lives and radiation qualities that can be applied for this purpose. An important task is to select a radionuclide that is compatible with the needs of a particular clinical application. The identification of the ideal targeted radiotherapeutic for each potential clinical application is a difficult task because of the multitude of variables that must be considered, some relating to the radioisotope, and others to the biological carrier. Hence it is recommended that a Co-ordinated Research Programme be established by the Agency to enable participants to acquire and intercompare the methodological expertise to evaluate the relative merit of therapeutic radiopharmaceuticals. These studies will be performed using a model system selected either from those described in this report or a promising agent that has emerged in the time since this meeting. The molecular carrier will be labelled with 131I, 125I as well as other therapeutic radionuclides available to the participant (for example, 90Y, 186Re, 188Re, 153Sm, 166Ho, 165Dy). The potential radiopharmaceuticals will then be compared in a progression of studies evaluating biological integrity after labelling, internalisation and residualization of radioactivity in the tumour cell, in vitro cytotoxicity, tissue distribution, normal organ toxicity (determination of the maximum tolerated dose) and finally, therapeutic efficacy

  8. Activity in the gastrointestinal tract after administration of bone-seeking radiopharmaceuticals. Experimental studies in mice

    Purpose: To test the possibility that (radio)activity of non-pertechnetate nature is excreted into the gastrointestinal tract at bone scintigraphy. Material and Methods: The distribution of a bone-seeking radiopharmaceutical (99mTc-HDP) was studied in an experimental mouse system by dissecting different organs and assessing their activity with a gamma-counter. Results: A comparison of the activity of the submandibular glands, which are assumed to accumulate only pertechnetate, and the gastrointestinal tract showed that a significant fraction of the activity excreted into the gastrointestinal tract did not consist of pertechnetate. Part of the excretion took place in the stomach. It was not connected to a specific bone-seeking agent or 99Mo/99mTc generator. Nor did it increase with time between make-up and injection. The excretion of the non-pertechnetate activity was reduced by cimetidine and omeprazole. These gastric-secretion blocking drugs did not reduce excretion of pertechnetate or significantly affect the general distribution of the radiopharmaceutical. Conclusion: There is a significant excretion of non-pertechnetate activity in the gastrointestinal tract. Part of this may be caused by excretion of the undegraded radiopharmaceutical by the stomach mucosa. (orig.)

  9. Overview of internal dose evaluation in the radiopharmaceutical production plant at IPEN

    Todo, Alberto S.; Gerulis, Eduardo; Cardoso, Joaquim C.S.; Rodrigues Junior, Orlando, E-mail: astodo@ipen.br, E-mail: rodrijr@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The internal dosimetry program at the Instituto de Pesquisas Energeticas e Nucleares, IPEN, is accomplished in two steps: the activity measurements are performed at the In Vivo Monitoring Laboratory and subsequently the data analysis and the dose evaluation are carried out by the Dose Calculation Group according to the ICRP models. The objective of this study is to take the whole body and thyroid monitoring results recorded from 2005 to 2015 to see whether the internal contamination control procedure for workers were suitable even with the increase in the radiopharmaceutical production. The study were based in a research called “Search of Variables” for the operations carried out in the restricted areas of radiopharmaceutical production plant, taking into account the dose distribution data for all the tasks recorded by the radioprotection service. This methodology aims to identify and determine the principal variables that impact on the worker's dose. The results were presented for the following variables: individual occupationally exposed, operation variable, area/cell, type of task of operation, which depend on the variable dose. In spite of growth rate in the production of radiopharmaceutical, this study has shown that the improvements in the plant have contributed to the dose reduction of the workers. (author)

  10. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors' 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy

  11. Species Dependence of [64Cu]Cu-Bis(thiosemicarbazone) Radiopharmaceutical Binding to Serum Albumins

    Basken, Nathan E.; Mathias, Carla J.; Lipka, Alexander E.; Green, Mark A.

    2008-01-01

    Introduction Interactions of three copper(II) bis(thiosemicarbazone) PET radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods 64Cu-labeled diacetyl bis(N4-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II) (Cu-PTSM), and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon, and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat, and mouse serum. Results The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/mL, “% Free” (non-albumin-bound) levels of radiopharmaceutical were 4.0 ± 0.1%; 5.3 ± 0.2%; and 38.6 ± 0.8% for Cu-PTSM; Cu-ATSM; and Cu-ETS, respectively. Conclusions Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans. PMID:18355683

  12. Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

    Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: 64Cu-labeled diacetyl bis(N4-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0±0.1%, 5.3±0.2% and 38.6±0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans

  13. Species dependence of [{sup 64}Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: nbasken@purdue.edu; Mathias, Carla J. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Lipka, Alexander E. [Department of Statistics, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

    2008-04-15

    Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated. Methods: {sup 64}Cu-labeled diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum. Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, '% free' (non-albumin-bound) levels of radiopharmaceutical were 4.0{+-}0.1%, 5.3{+-}0.2% and 38.6{+-}0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively. Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans.

  14. Radiological investigation in the outside area of expedition's room during radiopharmaceuticals' expedition

    Radiopharmaceuticals produced in IEN - Instituto de Engenharia Nuclear of the Brazilian Nuclear Energy Commission, are issued by the radiation protection team, which is responsible for preparing and issuing the packaged documentation required for movement in modal transportation. The documents are: Invoice , Shipper's Declaration of Radioactive Material , Shipper's Declaration of Dangerous Goods - (form IATA ) , Emergency Sheet, sketch of packed. All this documentation is inserted in an envelope of emergency. The Department of Radiological Protection is responsible for issuing such documents except the invoice that is issued by the Commercial Sector (Setcom). A employee of this sector is responsible for delivering it to the shipment sector. The preparation of packaged and documentation is performed in a room located in the building of Radiopharmaceutical Division. The vehicles which are used in the transport are parked outside this building, where are monitored after commissioning of packaged. The present study aims to evaluate potential and occupational radiation risks of people in transit or remain in the area where radioactive material circulates due to the shipment of radiopharmaceuticals for the classification of the area during the operation of dispatch

  15. Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

    The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [18F]FDG and [11C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).

  16. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    Adelstein, S.J. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Office of Sponsored Programs

    1995-02-01

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors` 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy.

  17. The role of high performance liquid chromatography in radiochemical/radiopharmaceutical synthesis and quality assurance

    This article discusses some specifications for HPLC methodology and reviews some recent applications of HPLC with emphasis on quality assurance (QA). Developments in the HPLC field will continue to find their way into practical everyday use in the radiopharmaceutical industry. This is illustrated in the area of column technology by the use of chiral columns for the determination of enantiomeric purity of receptor-based radiopharmaceuticals and by the use of internal surface reversed-phase (ISRP) columns for determination of radiolabelled metabolites in whole blood. An increased use of optimization and chemometric methods should provide better resolution in preparative and analytical procedures. Computer techniques applied to data manipulation could aid in the elimination of human bias in determining radiochemical purities and specific activities. If HPLC is to be adopted as a routine tool for the QC of radiopharmaceuticals, particularly those prepared in-house, more effort should be made to guarantee that proper standards are in place to assure compliance, especially as responsibilities are passed from the more highly trained senior level personnel to the technologist/technician level

  18. Medical application of nuclear science: nuclear medicine and production of radiopharmaceuticals

    Nuclear science in attendance on medicine or from Radium to Radiopharmaceuticals. By a brief historical reminder of the evolution of the radioactivity and development of nuclear science, we could see a very early interest and application of the radioactivity in the medical field. Main steps: Detection of natural radioactivity/Discovery of artificial radioactivity/First treatment of leukaemia and thyroid/First nuclear reactor/First radioisotope laboratory in hospital/First scintigraphy/First radiopharmaceutical/First cyclotron and cyclotron products/First immunoscintigraphy/Biotechnology and radioisotope/Evolution of technics [equipment for diagnosis (imaging, scintigraphy) and therapy]/Evolution of production technics and concept of products (generators of Technetium) and machines, reactor, cyclotron/Evolution of importance and interest of nuclear medicine/Creation of international association of nuclear medicine and producers (example ARPR)/Evolution of safety and pharmaceuticals regulation. After the sixties, period extremely rich in invention of products, characterized by a high fertility specially due to a non-restrictive regulation in terms of safety and pharmaceutical consideration, the evolution of technics, the importance of costs (investment, research, healthcare and the evolution of the regulations) have smoothly but continuously transformed the contexts and different actors. Consequences and facts: Rationalization and standardization of the catalogues, total integration of radiopharmaceuticals into the pharmaceutical laws, stop of nuclear research reactors, increase of number of cyclotrons, transformation of size and role of the producers and nuclear centers, risk in supply of some raw materials like Molybdenum, medical nuclear application as a worldwide business

  19. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1977-October 31, 1980

    Although the germanium-68 → gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available 68Ga/68Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than 68Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing 68Ga-radiopharmaceuticals. We have developed a new generator using a solvent extraction system which will produce 68Ga-oxine (8-hydroxyquinoline), a weak chelate. Using this agent we have synthesized several 68Ga-radiopharmaceuticals and tested them in vitro and in vivo. We have also carried out some preliminary studies to compare generator systems which produce 68Ga in an ionic form. Attempts have been made using polarographic and chromatographic techniques, and in vivo distribution data to investigate the stability of radiogallium complexes with a series of potentially lipophilic complexing agents

  20. Comparative study of radiopharmaceuticals as radiodiagnostic agent of cardiac damage in rats

    Six radiopharmaceuticals were screened in a small-animal model as potential infarct-localizing agents. The model used was subcutaneous inyection of isoproterenol (30 mg/kg of body weight) - induced myocardial lesions in rats, similar to an infarct and ischemia in human beings, corroborated by histological findings. The uptake of each radiopharmaceuticals is measured at various times after lesion initiation. The results are expressed as % I.D./g and through the contrast relations between the activity of whole heart of treated rats and the others tissues. The relation damaged heart/normal heart (DH/NH) of the phosphorated radiopharmaceuticals (sup(99m) Tc-PPi, sup(99m) Tc-MDP, sup(113m) In-EDTMP), and 197Hg-MPG are significatively greater in rats with heart damaged than in the controls animals (undamaged); these were followed by sup(99m) Tc-GH and sup(99m) Tc-DMSA. Sup(99m) Tc-PPi, was the tracer that showed the mot favorable concentration in the lesion and the best target-non target ratios in most of the time intervals. At early time intervals 197Hg-MPG showed the best DH/NH relation. (Author)

  1. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1977-October 31, 1980

    Welch, M.J.

    1980-06-01

    Although the germanium-68 ..-->.. gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available /sup 68/Ga//sup 68/Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than /sup 68/Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing /sup 68/Ga-radiopharmaceuticals. We have developed a new generator using a solvent extraction system which will produce /sup 68/Ga-oxine (8-hydroxyquinoline), a weak chelate. Using this agent we have synthesized several /sup 68/Ga-radiopharmaceuticals and tested them in vitro and in vivo. We have also carried out some preliminary studies to compare generator systems which produce /sup 68/Ga in an ionic form. Attempts have been made using polarographic and chromatographic techniques, and in vivo distribution data to investigate the stability of radiogallium complexes with a series of potentially lipophilic complexing agents.

  2. Determination of the influence factors of the radiopharmaceutical vials dimensions used for activimeter calibration at IPEN

    This paper presents the establishment of a quality control program and correction factors for the geometry of the vials used for distribution of radiopharmaceutical and activimeters calibration. The radiopharmaceutical produced by IPEN 67Ga, 131I, 201Tl and 99mTc had been tested using two different vials. Results show a maximum variation of 22% for 201Tl, and the minimum variation was 2.98% for 131I. The correction factors must be incorporated in the routine calibration of the activimeters. - Highlights: ► Establishement of quality control program for reference activimeters. ► Determination of correction factors for the geometry of vials. ► Radiopharmaceuticals tested for different vials were 67Ga, 131I, 201Tl and 99mTc. ► The maximum variation was 22% for 201Tl and the minimum variation was 2.98% for 131I. ► Correction factors must be incorporated in the calibration of the activimeters.

  3. Minimising activity and dose with enhanced image quality by radiopharmaceutical administrations

    Owing to the introduction of new diagnostic procedures, such as computed tomography (CT), positron emission tomography (PET) and single photon emission computed tomography (SPECT), the individual dose caused by medical exposures has grown rapidly in the last years. This is especially a subject to radiation protection for nuclear medical diagnosis, since in this case radiopharmaceuticals are administered to the patient, meaning not only a radiation exposure to the diseased tissue but also to the healthy tissues of large parts of the body. 'Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations' (MADEIRA) is a project co-funded by the European Commission within the Seventh Euratom Framework Programme that aims to improve three-dimensional (3D) nuclear medical imaging technologies significantly. MADEIRA is aiming to improve the efficacy and safety of 3D PET and SPECT functional imaging by optimising the spatial resolution and the signal-to-noise ratio, improving the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumorous and healthy tissues, and evaluation of the corresponding patient dose. Using an optimised imaging procedure that improves the information gained per unit administered dose, MADEIRA aims especially to reduce the dose to healthy tissues of the patient. In this paper, an overall summary of the current achievements will be presented. (authors)

  4. Efficiancy of hydrogen peroxide for cleaning production areas and equipments in the radiopharmaceutical production

    A great challenge in the radiopharmaceuticals production is to fulfill the Good Manufacturing Practices (GMPs), involving the validation of process and of all supporting activities such as cleaning and sanitization. The increasingly strict requirements for quality assurance system, with several norms and normative resolutions has led to a constant concern with programs and cleaning validation in pharmaceutical production. The main goal of GMP is to reduce risks inherent to pharmaceutical production, that is to reduce product contamination with microorganisms and cross-contamination. The basic requirements to prevent contamination is the development and implementation of efficient cleaning programs. In the case of clean rooms for the production of injectable radiopharmaceuticals, the requirement for cleaning programs is evidently higher due to the characteristics of these areas with hot cells for radioactive materials, where sterile radiopharmaceuticals are manipulated and distributed before administration to patients just after minutes or hours of its preparation. In the Radiopharmacy Department at IPEN it was established a cleaning program for clean rooms and hot cells using a hydrogen peroxide solution (20% proxitane alfa). The objective of this work was to assess effectiveness of this cleaning agent in reducing and/or eliminating microbial load in the clean rooms and equipment to acceptable levels in accordance with the current legislation. The analysis was conducted using results of the environmental monitoring program with and settling contact plates in clean rooms after the cleaning procedures. Furthermore, it was possible to evaluate the action of the sanitizing agent on the microbial population on the surface of equipment and clean rooms. It was also evaluated the best way to accomplish the cleaning program considering the dosimetric factor in each production process, as the main concern of pharmaceutical companies is the microbiological contamination, in

  5. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: 18F (109,7 min, 249,8 keV), 89Zr (78,4 hs, 395,5 keV), 11C (20,4 min, 385,7 keV) and 68Ga (67,8 min, 836 keV). 68Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism (18F-FDG), lipogenesis (11C-Choline and 11C-Acetate), amino acid transport (Anti-18F-FACBC), bone matrix (18F-NaF), prostatespecific membrane antigen (68Ga-PSMA and 89Zr-J591), CXCR receptors (89Ga-Pentixafor), adrenal receptors (18F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-18FFACBC (liver) and 18F-FBDC (stomach wall) are the exception. Higher effective dose was seen 18F-NaF (27 μSv/MBq) while the lowest was 11CAcetate (3,5 μSv/MBq). Conclusion: Even though 18F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when 18F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider 11C or 18F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for 18F labeling. Anti-18F-FACBC, 68Ga-PSMA and 68Ga-Pentixafor are demonstrating good results but more researches are needed. While PSMA imaging seems to be independent of PSA level, one choline

  6. Efficiancy of hydrogen peroxide for cleaning production areas and equipments in the radiopharmaceutical production

    Baptista, Tatyana S.; Batista, Vanessa; Gomes, Antonio; Matsuda, Margareth; Fukumori, Neuza; Araujo, Elaine B. de, E-mail: tsbaptista@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    A great challenge in the radiopharmaceuticals production is to fulfill the Good Manufacturing Practices (GMPs), involving the validation of process and of all supporting activities such as cleaning and sanitization. The increasingly strict requirements for quality assurance system, with several norms and normative resolutions has led to a constant concern with programs and cleaning validation in pharmaceutical production. The main goal of GMP is to reduce risks inherent to pharmaceutical production, that is to reduce product contamination with microorganisms and cross-contamination. The basic requirements to prevent contamination is the development and implementation of efficient cleaning programs. In the case of clean rooms for the production of injectable radiopharmaceuticals, the requirement for cleaning programs is evidently higher due to the characteristics of these areas with hot cells for radioactive materials, where sterile radiopharmaceuticals are manipulated and distributed before administration to patients just after minutes or hours of its preparation. In the Radiopharmacy Department at IPEN it was established a cleaning program for clean rooms and hot cells using a hydrogen peroxide solution (20% proxitane alfa). The objective of this work was to assess effectiveness of this cleaning agent in reducing and/or eliminating microbial load in the clean rooms and equipment to acceptable levels in accordance with the current legislation. The analysis was conducted using results of the environmental monitoring program with and settling contact plates in clean rooms after the cleaning procedures. Furthermore, it was possible to evaluate the action of the sanitizing agent on the microbial population on the surface of equipment and clean rooms. It was also evaluated the best way to accomplish the cleaning program considering the dosimetric factor in each production process, as the main concern of pharmaceutical companies is the microbiological contamination, in

  7. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    Fernandes, F [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil); Silva, D da [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Rodrigues, L [Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil)

    2015-06-15

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transport (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup

  8. Introduction to the use of FRAM on the effectiveness assessment of a radiopharmaceutical dispatches process

    This article aims to make an introduction to the use of Functional Resonance Analysis Method (FRAM) on the effectiveness assessment of a specific radiopharmaceutical dispatching process. The main purpose was to provide a didactic view of the method application to further in-depth analysis. The investigation also provided a relevant body of knowledge of radiopharmaceuticals dispatches processes. This work uses the term 'effectiveness assessment' instead of 'risk assessment' due to the broader meaning the former provide. The radiopharmaceutical dispatching process is the final task of a dynamic system designed to attend several medical facilities. It is comprised by functions involving mostly human activities, such as checking and packaging the product and measuring the radiopharmaceutical nuclear activity. Although the dispatch process has well-known steps for its completion, the human factor is the fundamental mechanism of work and control, being susceptible of irregular and instable performance. As a socio-technical system, the risk assessment provided by FRAM may be of importance for safety and quality improvements, even more if considered the nuclear nature of the product, which makes risk assessment critical and mandatory. A system is safe if it is resistant and resilient to perturbations. Identification and assessment of possible risks is, therefore, an essential prerequisite for system safety. Although this seems obvious, most risk assessments are conducted under relative ignorance of the full behavior of the system. Such condition has lead to an approach to assess the risks of intractable systems (i.e., systems that are incompletely described or under specified), namely Resilience Engineering. Into this area, the Functional Resonance Analysis Method has been developed in order to provide concepts, terminology and a set of methods capable of dealing with such systems. The study was conducted following the Functional Resonance Analysis Method. At first, the

  9. Multi-tracer syntheses at a radiopharmaceutical production centre 'A shift of paradigm'

    Full text: The positron emission tomography (PET) is an unique, non-invasive, powerful diagnostic tool at the forefront of modern functional imaging in clinical nuclear medicine. Traditionally PET is based on short-lived positron emitters ('11C 13N 15O, 18F) which are produced by low-energy cyclotrons. Due to the short half-live fast technical and chemical processes are essential for the production and the synthesis of the radiopharmaceuticals. Since not every PET center can afford to have an own production cyclotron the availability of the different PET tracers at the wide spread PET centers is limited. Furthermore, PET is widely established as a routine assessment of cancer, neurological disorders as well as coronary artery disease in humans and the diagnostic fields are rapidly growing with the development and demand of new bio tracers. At this point PET radiopharmaceutical production and distribution companies can serve such PET centers. The radionuclide 18F is suitable for long-distance distribution. The half-live of 109 min, fast synthesis times and high yields allow transportation of multiple dose vials over a 6 hours time range. This gives the possibility to operate cyclotron centers on a commercial base and distribute PET radiopharmaceuticals to hospitals and private doctors over a certain distance. In consequence, commercial radiopharmaceutical production centers are challenged to offer an high product diversity at high yield production and quality levels. Also highly optimised logistics are necessary to build up a satellite distribution system to cover the amount of activity needed for applications in PET centres away from the production site. In the present work an overview of the installation and the routine operation of ARGOS cyclotron and IASON Graz, two companies dedicated to the production and distribution of PET radiopharmaceuticals for the European market is given. It will reflect the problems of the daily production (e.g. coordination of the

  10. Cryptanalysis of Achterbahn-Version 1 and -Version 2

    Xiao-Li Huang; Chuan-Kun Wu

    2007-01-01

    Achterbahn is one of the candidate stream ciphers submitted to the eSTREAM, which is the ECRYPT StreamCipher Project. The cipher Achterbahn uses a new structure which is based on several nonlinear feedback shift registers(NLFSR) and a nonlinear combining output Boolean function. This paper proposes distinguishing attacks on Achterbahn-Version 1 and -Version 2 on the reduced mode and the full mode. These distinguishing attacks are based on linear approxi-mations of the output functions. On the basis of these linear approximations and the periods of the registers, parity checkswith noticeable biases are found. Then distinguishing attacks can be achieved through these biased parity checks. As toAchterbahn-Version 1, three cases that the output function has three possibilities are analyzed. Achterbahn-Version 2, themodification version of Achterbahn-Version 1, is designed to avert attacks based on approximations of the output Booleanfunction. Our attack with even much lower complexities on Achterbahn-Version 2 shows that Achterbahn-Version 2 cannotprevent attacks based on linear approximations.

  11. Versions Of Care Technology

    Sampsa Hyysalo

    2007-01-01

    Full Text Available The importance of users for innovation has been increasingly emphasized in the literatures on design and management of technology. However, less attention has been given to how people shape technology-in-use. This paper first provides a review of literature on technology use in the social and cultural studies of technology. It then moves to examine empirically how a novel alarm and monitoring appliance was appropriated in the work of home-care nurses and in the everyday living of elderly people. Analysis shows that even these technically unsavvy users shaped the technology considerably by various, even if mundane, acts of adapting it materially, as well as by attributing different meanings to it. However, the paper goes on to argue that such commonplace phrasing of the findings obscures their significance and interrelations. Consequently, the final section of the paper reframes the key findings of this study using the concepts of practice, enactment, and versions of technology to reach a more adequate description.

  12. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with technetium-99m and on the bioavailability of radiopharmaceuticals

    Maria Luisa Gomes

    2002-09-01

    Full Text Available The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with technetium-99m (99mTc and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural consequence is a correct diagnosis. However, when it is unknown, it is undesirable and the consequences are the possibility of misdiagnosis and/or the repetition of the examination with an increase of radiation dose to the patient. The possible explanation to the appearance of DIR are (a radiopharmaceutical modification, (b alteration of the labeling efficiency of the radiopharmaceutical, (c modification of the target, (d modification of no target and/or the (e alteration of the binding of the radiopharmaceutical on the blood proteins. The effect of drugs on the labeling of blood elements with 99mTc might be explained by (i a direct inhibition (chelating action of the stannous and pertechnetate ions, (ii damage induced in the plasma membrane, (iii competition of the cited ions for the same binding sites, (iv possible generation of reactive oxygen species that could oxidize the stannous ion and/or (v direct oxidation of the stannous ion. In conclusion, the development of biological models to study the DIR is highly relevant.A evidência de que drogas naturais ou sintéticas podem afetar a radiomarcação ou a biodisponibilidade de radiofármacos nos procedimentos de medicina nuclear já é bem conhecida. Entretanto, essa interação de droga com radiofármacos (IDR não está completamente compreendida. Vários autores têm descrito o efeito de drogas na marcação de elementos sanguíneos com tecnécio-99m (99mTce na biodistribuição de radiofármacos. Quando a

  13. Synthesis, labeling with 99mTc and biokinetics of brains scintigraphy diaminodithiol perfusion radiopharmaceuticals

    The recent tomography status using radiopharmaceuticals have been contributing greatly with the 'age of certainty' in the diagnosis examination of syndromes, pathologies and clinical signs, because they can evidence some phenomena occurring in a molecular manner. The purpose of this work have had the development of new diaminodithiol (DADT) perfusion radiopharmaceuticals to be used in brain diagnosis using S.P.E.T. (Single Photon Emission Tomography). Initially, the rational planning had been performed with the new DADT molecular structures as radiopharmaceutical candidates. Using of Q.S.A.R. (Quantitative Structure Activity Relationship) techniques, the molecular descriptors such as partition coefficient and effective polarizability, have been studied in order to increase the blood brain barrier transport and the brain uptake respectively. Applying the Q.S.P.R. (Quantitative Structure Property Relationship) concepts to perform drug latentiation, based on bio-labile functional groups, the congener DADT derivative has been transformed into a pro-drug that works as a DADT moiety carrier, allowing the increasing of brain radiopharmaceutical uptake. Later on, synthetic routes and chemical purifications have been developed allowing the creation of the proposed chemical structure. Each new DADT derivative has been synthesized and analyzed in terms of elemental analysis, infrared and NMR spectra, in order to confirm its proposed chemical structure. Then, the new derivative has been labeled with 99mTc, radiochemically purified, intravenously injected in Swiss mice, allowing its biodistribution to evidence its brain transport and uptake. The rational planning studies have been re-evaluated after each biodistribution had been performed, to see what kind of molecular descriptor was responsible for causing a stronger optimization in the brain perfusion characteristics and then, new DADT derivatives have been prepared. Three new DADT derivatives have been obtained by using QSAR

  14. Use of technegas as a radiopharmaceutical for the measurement of gastric emptying

    Many radiopharmaceuticals and test meals that are used to measure gastric emptying are less than optimal. A vegetable-based solid meal, such as rice, labelled with a radiopharmaceutical that also has the capacity to measure gastric emptying of liquids, is likely to be ideal. The role of Technegas as a radioisotopic marker to measure gastric emptying of rice and liquids was evaluated. Technegas-labelled rice was incubated in 0.9% saline, 1 M HCl and simulated gastric fluid (3.2 g/l pepsinogen, pH 2-3) to assess stability of the label. In eight healthy volunteers gastric emptying of two meals - 200 g rice (370 kcal) and 75 g dextrose dissolved in 300 ml water (300 kcal), both labelled with 20 MBq of Technegas - was measured scintigraphically. Over 4 h, the average label stability was 93.7%±0.5% in 0.9% saline, 91.0%±0.4% in 1 M HCl and 93.6%±0.7% in simulated gastric juice. The lag phase was longer for rice than dextrose (25±7 min vs 4±2 min; P<0.05), but there was no difference in the post-lag emptying rate (2.1±0.3 kcal/min vs 1.7±0.2 kcal/min; P=0.2) between the two meals. We conclude that Technegas is a suitable radiopharmaceutical for measurement of gastric emptying of rice and nutrient-containing liquids. (orig.)

  15. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    Silveira, Marina B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Dias, Consuelo L. Fortes [Fundacao Ezequiel Dias (FUNED), Belo Horizonte, MG (Brazil)], e-mail: consuelo@pq.cnpq.br; Cassali, Geovanni D. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada], e-mail: cassalig@icb.ufmg.br

    2009-07-01

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  16. Binding studies of the antitumoral radiopharmaceutical 125I-Crotoxin to Ehrlich ascites tumor cells

    The development of tools for functional diagnostic imaging is mainly based on radiopharmaceuticals that specifically target membrane receptors. Crotoxin (Crtx), a polypeptide isolated from Crotalus durissus terrificus venom, has been shown to have an antitumoral activity and is a promising bioactive tracer for tumor detection. More specific radiopharmaceuticals are being studied to complement the techniques applied in the conventional medicine against breast cancer, the most frequent cause of death from malignant disease in women. Crtx's effect has been shown to be related with the overexpression of epidermal growth factor receptor (EGFR), present in high levels in 30 to 60% of breast tumor cells. Our objective was to evaluate Crtx as a tracer for cancer diagnosis, investigating its properties as an EGFR-targeting agent. Ehrlich ascites tumor cells (EAT cells) were used due to its origin and similar characteristics to breast tumor cells, specially the presence of EGFR. Crtx was labeled with 125I and binding experiments were performed. To evaluate the specific binding in vitro of Crtx, competition binding assay was carried out in the presence of increasing concentrations of non-labelled crotoxin and epidermal growth factor (EGF). Specific binding of 125I-Crtx to EAT cells was determined and the binding was considered saturable, with approximately 70% of specificity, high affinity (Kd = 19.7 nM) and IC50 = 1.6 x 10-11 M. Our results indicate that Crtx's interaction with EAT cells is partially related with EGFR and increases the biotechnological potential of Crtx as a template for radiopharmaceutical design for cancer diagnosis. (author)

  17. A generic model for 11C labelled radiopharmaceuticals for imaging receptors in the human brain

    A large number of radiopharmaceuticals labelled with 11C (half-time 0.340 h) are being developed for positron emission tomographic studies of different types of receptor in the human brain. For most of these agents the available biokinetic data are insufficient to construct realistic compound-specific biokinetic models for calculating the internal radiation dose delivered to persons undergoing investigation. A generic model for brain receptor substances that predicts the internal dose with sufficient accuracy for general radiation protection purposes has, therefore, been developed. Biokinetic data for 13 11C radiopharmaceuticals used clinically for imaging different brain receptors indicate that, despite differences in chemical structure, their uptake and retention in the human brain and other tissues is broadly similar. The proposed model assumes instantaneous deposition of 5% of the injected radioactivity in the brain, with the remaining radioactivity being rapidly and uniformly distributed throughout all other tissues. Elimination from all tissues is assumed to occur with a half-time of 2 h. It is further assumed that 75% of the injected 11C is excreted in the urine, and 25% via the gall bladder, with a half-time of 2 h. This model yields an effective dose of 4.5 x 10-3mSv/MBq, with doses of 3.2 x 10-2, 1.7 x 10-2, 8.7 X 10-3, 5.2 x 10-3, and 3.8 x 10-3mGy MBq-1 to the urinary bladder, gall bladder, kidneys, brain and ovaries, respectively. These doses are well within the range of those reported using compound-specific models for the radiopharmaceuticals studied. (author)

  18. Eye lens dosimetry in workers of a PET radiopharmaceutical production facility

    Guimaraes, M. C.; Lacerda, M. A. S.; Da Silva, T. A. [Development Center of Nuclear Technology, Posgraduate Course in Science and Technology of Radiations, Minerals and Materials, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil); Meireles, L. S.; Teles, L. L. D., E-mail: margaretecristinag@gmail.com [Development Center of Nuclear Technology / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: A new regulatory statement was issued concerning the eye lens radiation protection of persons in some planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the dosimetry procedure with the Eye-D{sup TM} holder with a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of the Development Center of Nuclear Technology (DCNT) Positron-Electron Tomography (PET) Radiopharmaceuticals Production Facility (RPF). The eye lens dosimeter was calibrated and its energy response was studied in terms Hp(3) on a ISO standard slab phantom and on a recent suggested cylindrical phantom. Irradiations were carried out at the DCNT Dosimeter Calibration Laboratory in ISO reference radiations of {sup 137}Cs gamma, narrow spectrum series X-ray beams, {sup 90}Sr/{sup 90}Y and {sup 85}Kr beta rays. Fifteen workers of the RPF/DCNT were monitored during radiopharmaceutical production activities (e.g. cyclotron operation, quality control tests, radiopharmaceutical production and radioprotection). Considering the predominant exposure to 511 keV photons, the energy dependence of the dosimeter of 30% in energies down to 33 keV should not be a concern. Calibration coefficient of the dosimeter in {sup 137}Cs beam showed that the use of the slab phantom will underestimate the Hp(3) in 8.8% related to the cylindrical phantom. The absorbed dose due to beta radiation exposure seems to be unfeasible to be assessed with the chosen dosimeter. Results showed that the workers responsible for quality control tests received the highest doses and that there is room for optimization. (Author)

  19. Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation

    Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDA's LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the 131I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the lyophilized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL-1 (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL-1, to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products 131I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get valuable quantitative and

  20. Assessment of occupational hazard in handling syringes containing radiopharmaceuticals, using Monte Carlo technique

    In recent years, the use of various radionuclides in nuclear medicine has increased significantly. Determination of true radiation exposure received by the hands of technologists handling radiopharmaceuticals is essential in order to confirm that the exposure is within the acceptable limits. A Monte Carlo computer code has been developed to calculate absorbed dose rates at surface sites on unshielded syringes containing radiopharmaceuticals for diagnostic and therapeutic injections. The code includes dose due to characteristic x-rays, gamma rays, beta particles and secondary electrons, and makes allowances for absorption in source and syringe wall region. The system used in the code consisted of radioactive fluid, plastic syringe and skin-tissue surrounding it. Water was taken as tissue-equivalent material and the syringe-barrel as a right circular cylinder. The code provides both axial and radial dose distribution at various locations in the skin and can handle various types and sizes of syringes, different amount, activity and type of radiopharmaceutical. Test cases were run for commonly used Technetium-99m on IBM 370/145 computer for 100,000 histories. Results using 1 ml (4.6mm I.D., 6.6mm O.D.) and 5 ml (12.8mm I.D., 14.4mm O.D.) fully filled syringes were 35-68 and 20-30 mrad/mCi-minute respectively, to the active layers of fingertips. Dose rates to the palm and wrist were much smaller. It was evaluated that fingertips of a technologist can receive 70-250 rems/year by performing 25 administrations per week (40 working week in a year) of 10 mCi activity each, when average administration time was 25 seconds. Similar results using the code can be utilized to determine the possible occupational risks in using unshielded syringes and to design an appropriate shield to avoid undesirable effect of excessive and unnecessary radiation exposure. (author)

  1. Use of technegas as a radiopharmaceutical for the measurement of gastric emptying

    Kwiatek, M.A. [School of Medical Radiation, University of South Australia, Adelaide (Australia); Jones, K.L. [School of Medical Radiation, University of South Australia, Adelaide (Australia)]|[Department of Medicine, Royal Adelaide Hospital, The University of Adelaide, Adelaide (Australia); Burch, W.M. [John Curtin School of Medical Research, Australian National University, Australian Capital Territory (Australia); Horowitz, M. [Department of Medicine, Royal Adelaide Hospital, The University of Adelaide, Adelaide (Australia); Bartholomeusz, F.D.L. [Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide (Australia)

    1999-08-01

    Many radiopharmaceuticals and test meals that are used to measure gastric emptying are less than optimal. A vegetable-based solid meal, such as rice, labelled with a radiopharmaceutical that also has the capacity to measure gastric emptying of liquids, is likely to be ideal. The role of Technegas as a radioisotopic marker to measure gastric emptying of rice and liquids was evaluated. Technegas-labelled rice was incubated in 0.9% saline, 1 M HCl and simulated gastric fluid (3.2 g/l pepsinogen, pH 2-3) to assess stability of the label. In eight healthy volunteers gastric emptying of two meals - 200 g rice (370 kcal) and 75 g dextrose dissolved in 300 ml water (300 kcal), both labelled with 20 MBq of Technegas - was measured scintigraphically. Over 4 h, the average label stability was 93.7%{+-}0.5% in 0.9% saline, 91.0%{+-}0.4% in 1 M HCl and 93.6%{+-}0.7% in simulated gastric juice. The lag phase was longer for rice than dextrose (25{+-}7 min vs 4{+-}2 min; P<0.05), but there was no difference in the post-lag emptying rate (2.1{+-}0.3 kcal/min vs 1.7{+-}0.2 kcal/min; P=0.2) between the two meals. We conclude that Technegas is a suitable radiopharmaceutical for measurement of gastric emptying of rice and nutrient-containing liquids. (orig.) With 2 figs., 16 refs.

  2. Eye lens dosimetry in workers of a PET radiopharmaceutical production facility

    Full text: A new regulatory statement was issued concerning the eye lens radiation protection of persons in some planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the dosimetry procedure with the Eye-DTM holder with a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of the Development Center of Nuclear Technology (DCNT) Positron-Electron Tomography (PET) Radiopharmaceuticals Production Facility (RPF). The eye lens dosimeter was calibrated and its energy response was studied in terms Hp(3) on a ISO standard slab phantom and on a recent suggested cylindrical phantom. Irradiations were carried out at the DCNT Dosimeter Calibration Laboratory in ISO reference radiations of 137Cs gamma, narrow spectrum series X-ray beams, 90Sr/90Y and 85Kr beta rays. Fifteen workers of the RPF/DCNT were monitored during radiopharmaceutical production activities (e.g. cyclotron operation, quality control tests, radiopharmaceutical production and radioprotection). Considering the predominant exposure to 511 keV photons, the energy dependence of the dosimeter of 30% in energies down to 33 keV should not be a concern. Calibration coefficient of the dosimeter in 137Cs beam showed that the use of the slab phantom will underestimate the Hp(3) in 8.8% related to the cylindrical phantom. The absorbed dose due to beta radiation exposure seems to be unfeasible to be assessed with the chosen dosimeter. Results showed that the workers responsible for quality control tests received the highest doses and that there is room for optimization. (Author)

  3. Fluorine-18 radiopharmaceuticals beyond [{sup 18}F]FDG for use in oncology and neurosciences

    Coenen, H.H. [Institut fuer Neurowissenschaften und Medizin, INM-5: Institut fuer Nuklearchemie, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany); Elsinga, P.H. [Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Hanzeplein 1, Groningen (Netherlands); Iwata, R. [Cyclotron and Radioisotope Center, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Kilbourn, M.R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, 2276 Medical Science I Building, Ann Arbor, MI 48109 (United States); Pillai, M.R.A., E-mail: m.r.a.pillai@iaea.or [Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Wagramer Strasse 5, A-1400 Vienna (Austria); Rajan, M.G.R. [Radiation Medicine Centre, Bhabha Atomic Research Centre, TMH Annexe, Parel, Mumbai 400012 (India); Wagner, H.N. [School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205-2179 (United States); Zaknun, J.J. [Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Wagramer Strasse 5, A-1400 Vienna (Austria)

    2010-10-15

    Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ({sup 18}F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the {sup 18}F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful {sup 18}F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of {sup 18}F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of {sup 18}F-tracers for oncology and neurosciences. A selection of three groups of {sup 18}F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on 'Development of {sup 18}F radiopharmaceuticals (beyond [{sup 18}F]FDG) for use in oncology and neurosciences' in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more {sup 18}F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

  4. Follow-up of radiopharmaceuticals out of globally harmonized system (G.H.S.) at the C.H.U. of Grenoble

    The improvement and the secure of the radiopharmaceutical circuit in the service of nuclear medicine of the Grenoble C.H.U. are a permanent concern and a true team work between the doctors and the pharmacists. The implementation of cards allowed to optimize the radiopharmaceuticals management by avoiding expenses in relation with the non given drugs. (N.C.)

  5. Harvard-MIT research program in short-lived radiopharmaceuticals. Progress report, September 1, 1980-February 28, 1982

    The investigators involved in this research proposal are engaged in a broad program of research designed to elucidate the basic chemistry of technetium. By synthesizing and isolating coordination compounds at macro concentrations using the radionuclide Tc-99, we are establishing a profile of ligand preferences and stereochemistry in a variety of oxidation states. As the systematics of the chemistry emerge, the knowledge is being applied to the design of radiopharmaceuticals labeled with the shortlived radionuclide Tc-99m. This progress report outlines work done in two specific areas which have been identified as being potentially useful in radiopharmaceutical chemistry. The first is a study of ligand exchange reactions which may lead to indirect syntheses for radiopharmaceuticals, and the second the application of high pressure liquid chromatography for the separation of complexes at both carrier and no carrier added concentrations

  6. The Radiopharmaceuticals Production and Research Centre established by the Heavy Ion Laboratory of the University of Warsaw

    Choiński, J.; Jastrzębskia, J.; Kilian, K.; Mazur, I.; Napiorkowski, P. J.; Pękal, A.; Szczepaniak, D.

    2014-03-01

    The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- ). Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centre's activities will also be devoted to the production of known species for preclinical studies and research into innovative radiopharmaceuticals in collaboration with other scientific units of this Campus as well as with members of the Warsaw Consortium for PET Collaboration. Research into the accelerator production route of 99mTc will also begin shortly.

  7. The Radiopharmaceuticals Production and Research Centre established by the Heavy Ion Laboratory of the University of Warsaw

    Choiński J.

    2014-03-01

    Full Text Available The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- . Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centre’s activities will also be devoted to the production of known species for preclinical studies and research into innovative radiopharmaceuticals in collaboration with other scientific units of this Campus as well as with members of the Warsaw Consortium for PET Collaboration. Research into the accelerator production route of 99mTc will also begin shortly.

  8. Quality assurance considerations related to open-quotes in-houseclose quotes radiopharmaceutical preparations utilizing positron emitting radionuclides

    The FDA oversees the clinical investigation of new and investigational drugs, including short lived radiopharmaceuticals, as well as monitors the use of these in basic research protocols through the activities of the approved Radioactive Drug Research Committee. Concurrent with the technical improvements being made in imaging techniques such as Positron Emission Tomography (PET) is the increasing availability of a variety of radiolabelled substrates possessing the unique potential to serve as indicators of in vivo alteration of biochemical processes. In order to comply with regulatory requirements for open-quotes in-houseclose quotes manufactured radiopharmaceuticals, the safety of the formulated products and the standards of the manufacturing facility must be clearly demonstrated through information provided to the regulatory agency. Difficult challenges to the investigators include not only qualitative identification but also quantitation of various impurity levels. The synthesis of two fluorine-18 labeled radioligands will serve to emphasize the detailed efforts being made to provide a finished radiopharmaceutical

  9. Guideline for in vivo diagnosis and therapy with radiopharmaceuticals - a comment

    Important rules and regulations included in guidelines for in vivo diagnosis and therapy with radiopharmaceuticals are described and commented comprehensively. Emphasis is laid on protection of patients, medical personnel, and the environment from harmful radiation effects. This is to be achieved through quality assurance and organisational provisions that must be observed during medical care and on discharge of patients from hospital treatment. Unambiguous definition of responsibilities of authorised medical specialists, non-medical graduates and technicians is expected to enhance legal security in applied nuclear medicine. (author)

  10. Preparation and biological distribution of some radiopharmaceutical compounds for human application

    Application of radiopharmaceutical for diagnostic purposes in egypt has increased so rapidly in the last few yeas that now most of the organs of the body could be imaged or scanned using a wide range of radiopharmaceuticals. Technetium - 99m labelled compounds are considered as the most widely spread radiopharmaceuticals which find wide applications in the area of nuclear medicine for either dianostic or therapeutic purposes. Among the important types of radiopharmaceuticals used for diagnostic purposes are the technetium - 99m labelled compounds of human serum albumin (HSA) in all its physical forms. The main objective of this thesis is to elucidate and investigate the best conditions for the preparatiion of followings: 1 - Technetium - 99m HSA which is widely used for blood pool, cardiac and placenta scanning. 2 - Tecnetium 99m HSA microsphere which are used for lung perfusion imaging, regional blood flow, cerebral perfusion imaging and reticuloendothelial system structure and function. 3 - Technetium - 99m HSA macroaggregate which is used for perfusion scintigraphy of the lung that is accomplished by microembolization of radionuclide - labelled particales in the pulmonary arterial circulation. Such particulate material embolization causes a minor obstruction to pulmonary arterial blood flow, but this effect is almost never physiologically significant . the number of particles which impact in a particular volume of the lung is proposional to the pulmonary arterial blood flow to that reason. Perfusion scintigraphy thus provides a visual representation of the relative distribution of pulmonary blood flow at the time of MAA injection.In all the previous preparations transchelation technique has been utilized using different co-ligands to overcome the problem of low affinity of HSA to the reduced technetium - 99m. The aim was planned to be achieved in the folllowing three chapters where detailed studies on the factors affecting the preparation of technetium -99m HSA

  11. Gallium-67 citrate an alternative radiopharmaceutical to111In DTPA for colonic transit studies

    Indium DTPA is the current radiopharmaceutical of choice for the evaluation of colonic transit in constipated patients. Its drawback encouraged the authors to look for an alternative tracer. It was found that gallium-67 citrate is versatile starting material for the preparation of many gallium complexes. Because of its lack of absorption from the gastro-intestinal tract, it has the following advantages over indium DTPA as a radioactive colonic transit marker: it is readily available, and being less than $1/MBq compared to $40/MBq, savings of up to $700 can be achieved per patient study. 5 refs., 2 tabs., 7 figs

  12. Guidance for the management of solid waste contaminated by urine of patients after administration of radiopharmaceuticals

    The recent reinforcement of the French regulation on radionuclide contaminated waste brings the Nuclear Medicine Departments in charge of writing guidance intended to the personnel of the health care units. A special attention must be paid to the waste contaminated by urine of the incontinent patients. The present paper provides time duration for the collection and the storage of urine contaminated waste obtained from the simulation with literature models and data for the most frequently used radiopharmaceuticals. The validity of the results is discussed according to the parameter variations of the biokinetic models. (authors)

  13. Receptor-specific positron emission tomography radiopharmaceuticals: 75Br-labeled butyrophenone neuroleptics

    Cerebral dopaminergic D2 receptors are involved in several common disease states, such as schizophrenia, Parkinson's disease, and Huntington's chorea. The use of radiolabeled D2 receptor-binding ligands with positron emission tomography (PET) to noninvasively quantitate D2 receptor densities thus has potential application in medicine. Butyrophenone neuroleptics have a high in vitro and in vivo binding affinity for cerebral D2 receptors, and due to the useful chemical and nuclear decay properties of 74Br (76% β+, half-life = 1.6 h), the authors have evaluated radiobrominated bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP) as radiopharmaceuticals for use with PET

  14. Control flow of radiopharmaceuticals in nuclear medicine by means of an E-service

    The almost generalized use of single-dose Nuclear Medicine for performing diagnostic tests or treatments, and the consequent complexity that accompanies its management, has resulted in the need to control the flow of material radioisotopic tools. An e-service is designed to manage the flow of radiopharmaceuticals and control its use and spending. This control does not only affect the efficiency in the use and cost of material, but in the radioactive waste associated with the non-use and waste reduction and a more effective organization of the Department. (Author)

  15. Knowledge evaluation for knowledge management implementation: A case study of the radiopharmaceutical centre of IPEN

    In recent years, organisations have used multiple methods and approaches to design their strategic and action plans. In this context, resource-based view (RBV) and knowledge-based view (KBV) frameworks have received increased attention as being instrumental to strategy formulation. The synergy of these approaches with knowledge management initiatives is intuitive and their use in a common framework is discussed here to show the importance of methods and instruments to mapping and assessing the knowledge assets of an organisation. The application of such methods to the radiopharmaceutical centre of IPEN is described. (author)

  16. Current status of PET imaging of differentiated thyroid cancer with second generation radiopharmaceuticals

    Although the prognosis of differentiated thyroid cancer (DTC) is favorable, some histotypes show worst clinical outcome and higher risk of recurrence. Serum thyroglobulin (Tg) levels and 131I-whole-body-scan (WBS), together with neck ultrasound (US), represent the golden standard for DTC follow-up. Nevertheless, the relatively high frequency of patients with high Tg levels and negative WBS requires further investigations by using new imaging modalities. The availability of whole body positron emission tomography (PET) methods, in parallel with the advances in radiochemistry, offer a wide substrate for many solutions. To this day 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT still represents the imaging of choice in follow-up of patients with high serum Tg and negative 131I-WBS but in the last decades the research has focused on finding “second generation” radiopharmaceuticals for PET imaging, with both diagnostic and prognostic purposes, aiming to change the way to image thyroid cancer. Moreover, the use of various PET radiopharmaceuticals, that offer the possibility to explore different pathways involved in thyroid cancer, could find important applications in the near future for clinical decision making in order to program tailored treatments and follow-up. It would be desirable to use the same radiopharmaceutical for both imaging and dosimetric purpose to achieve a tailored therapy. Many efforts are focused in this direction and 124I-PET/CT is now emerging as a valid tool in restaging and therapy management of DTC with promising results. Although the preliminary data available in literature require a confirmation in larger studies with longer follow-up, we think that in next future 124-PET/CT could gain an important role for management of DTC. The aim of this review was to perform a systematic analysis of literature describing the state of art of “second generation” PET-radiopharmaceuticals for imaging DTC. Discussion is focused on the utility of 124I

  17. Therapeutical radiopharmaceuticals based In vivo generator system [166 Dy] Dy/166 Ho

    At the idea to administer to a patient a molecule containing in it structure a father radionuclide, with a half life enough large which allows to the radiolabelled molecule to take up position specifically in a white tissue and decaying In vivo to the daughter radionuclide with properties potentially therapeutic, it is known as In vivo generator system. In this work the preparation and the preliminary dosimetric valuations of radiopharmaceuticals based In vivo generator system 166 Dy Dy/166 Ho for applications in radioimmunotherapy, in the treatment of the rheumatoid arthritis and in the bone marrow ablation (m.o.) for candidates patients to bone marrow transplant are presented. (Author)

  18. 90Y-preparation and some preliminary results on labelling of radiopharmaceuticals

    The production of 90Y by 90Sr-90Y generator was studied. 90Sr was adsorbed at a column with Aminex A-5 resin. The daughter radionuclide 90Y was eluted with 0.7 M α-hydroxyisobutyrate (α-HIB, pH5.4). Radionuclidic, radiochemical and chemical purities were >98% and yield >85%. After converting into chloride form 90YCl3-solution (pH:1) was used for preparing injectable yttrium citrate and labelling some other radiopharmaceuticals such as antibody or methylene diphosphonate (MDP). Furthermore, a fast ITLC-method for determination the content of 90Sr in 90Y-eluate was developed. (author)

  19. Development of Therapeutic Radiopharmaceuticals Based on 90Y Biotin. Chapter 7

    The preparation of a biotin derivative labelled with 90Y to be employed as a breast cancer therapeutic radiopharmaceutical in the application of the new IART approach is described in this chapter. The effects of pH on the labelling yield and in vitro affinity for avidin of the resulting radiolabelled conjugate are evaluated. Radiolabelling was performed using a manual and an automated procedure, and radiation exposure was measured for each operational condition. Microbiological tests were conducted on each final batch after decay of activity. Results obtained from a first clinical study are also described. (author)

  20. USCEA/NIST measurement assurance programs for the radiopharmaceutical and nuclear power industries

    Golas, D.B. [Council for Energy Awareness, Washington, DC (United States)

    1993-12-31

    In cooperation with the U.S. Council for Energy Awareness (USCEA), the National Institute of Standards and Technology (NIST) supervises and administers two measurement assurance programs for radioactivity measurement traceability. One, in existence since the mid 1970s, provides traceability to suppliers of radiochemicals and radiopharmaceuticals, dose calibrators, and nuclear pharmacy services. The second program, begun in 1987, provides traceability to the nuclear power industry for utilities, source suppliers, and service laboratories. Each program is described, and the results of measurements of samples of known, but undisclosed activity, prepared at NIST and measured by the participants are presented.