J A Tafani

IPBS - Institut de Pharmacologie et de Biologie Structurale , Toulouse, Midi-Pyrenees, France

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Publications (20)48.79 Total impact

  • Article: Structure-activity relationships of neuropeptide FF: role of C-terminal regions.
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    ABSTRACT: A structure-activity study was carried out to determine the importance of the C-terminal amino acids of the octapeptide Neuropeptide FF (NPFF) in binding and agonistic activity. Affinities of NPFF analogues were tested toward NPFF receptors of the rat spinal cord and the human NPFF2 receptors transfected in CHO cells. The activities of these analogues were evaluated by their ability to both inhibit adenylate cyclase in NPFF2 receptor transfected CHO cells and to reverse the effect of nociceptin on acutely dissociated rat dorsal raphe neurons. The substitutions of Phenylalanine8 by a tyrosine, phenylglycine or homophenylalanine were deleterious for high affinity. Similarly, the replacement of Arginine7 by a lysine or D. Arginine induces a loss in affinity. The pharmacological characterization showed that the presence of the amidated Phe8 and Arg7 residues are also extremely critical for activation of anti-opioid effects on dorsal raphe neurons. The sequence of the C-terminal dipeptide seems also to be responsible for the high affinity and the activity on human NPFF2 receptors. The results support the view that a code messaging the molecular interaction toward NPFF-receptors is expressed in the C-terminal region of these peptides but the N-terminal segment is important to gain very high affinity.
    Peptides 10/2001; 22(9):1471-8. · 2.43 Impact Factor
  • Article: [(125)I]EYF: a new high affinity radioligand to neuropeptide FF receptors.
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    ABSTRACT: [(125)I]EYF ([(125)I]EYWSLAAPQRFamide), a new radioiodinated probe derived from a peptide present in the rat Neuropeptide FF precursor (EFWSLAAPQRFamide, EFW-NPSF) was synthesized and its binding characteristics investigated on sections of the rat spinal cord and on membranes of mouse olfactory bulb. In both tissues, [(125)I]EYF binding was saturable and revealed a very high affinity interaction with a single class of binding sites in rat and mouse (K(D) = 0.041 and 0.019 nM, respectively). Competition studies showed that [(125)I]EYF bound to one class of binding sites exhibiting a high affinity for all the different peptides the precursor could generate (NPA-NPFF, SPA-NPFF, NPFF, EFW-NPSF, QFW-NPSF) with the exception of NPSF which displayed a low affinity. Autoradiographic studies demonstrated that [(125)I]EYF binding sites were fully inhibited by a synthetic Neuropeptide FF agonist (1DMe) in all areas of the rat brain. The density of [(125)I]EYF binding sites was high in the intralaminar thalamic nuclei, the parafascicular thalamic nucleus and in the superficial layers of the dorsal horn. Non specific binding reached 5-10% of the total binding in all brain areas. Similarly, in mouse brain experiments, the non-specific binding was never superior to 10%. These findings demonstrate that putative neuropeptides generated by the Neuropeptide FF precursor and containing the NPFF or NPSF sequences should bind to the same receptor. Furthermore, these data indicate that [(125)I]EYF is a useful radiolabeled probe to investigate the NPFF receptors; its major advantages being its high affinity and the very low non-specific binding it induces.
    Peptides 05/2001; 22(4):623-9. · 2.43 Impact Factor
  • Article: A radioiodinated 7alpha-O-iodoallyl diprenorphine for mapping opioid receptors.
    R F Wang, J A Tafani, J M Zajac, R Guiraud
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    ABSTRACT: The aim of the current research has been to validate an original radioiodinated diprenorphine (DPN) derivative suitable for imaging studies of opioid receptors. [(125)I]7alpha-O-iodoallyl diprenorphine (7alpha-O-IA-DPN) was prepared by radioiododestannylation and in vitro and in vivo opioid receptor binding assays were performed with CDF1 mouse brains. In vitro binding studies showed high affinity (K(i)= 0.4 +/- 0.2 nM) for mouse brain membranes. In vivo studies showed 63% specific binding. Ex vivo autoradiography of brain sections confirmed high uptake and retention of [(125)I]7alpha-O-IA-DPN in regions rich in opioid receptors. This new radioiodinated DPN analogue appears to be a potential radioprobe for in vivo visualization of human cerebral opioid receptors with single photon emission computed tomography (SPECT).
    Neuropeptides 01/2000; 33(6):498-502. · 1.55 Impact Factor
  • Article: Characterization of a new radioiodinated probe for the alpha2C adrenoceptor in the mouse brain.
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    ABSTRACT: [125I]17alpha-hydroxy-20alpha-yohimban-16beta-(N-4-p6 hydroxyphenethyl)carboxamide or [125I]rauwolscine-OHPC, a new radioiodinated probe derived from rauwolscine was synthesized and its binding characteristics investigated on sections of the mouse caudate putamen. [125I]rauwolscine-OHPC binding was saturable and revealed interaction with a single class of binding sites (KD= 0.171 nM, Bmax = 3082 pCi/mg of tissue). The kinetically derived affinity was in close agreement with the affinity evaluated by saturation experiments: k(-1)/k(+1)(0.0403 min(-1)/114 10(6) M(-1) min(-1))=0.35 nM. Competition studies revealed interaction with one single class of binding sites for each of the twelve compounds tested. The rank of potency suggested an interaction with alpha2 adrenoceptors (atipamezole > or = RX 821002 > yohimbine > (-)epinephrine). Moreover, the good affinity of [125I] rauwolscine-OHPC binding sites for spiroxatrine, yohimbine, WB 4101, the relatively good affinity for prazosin (Ki =37.4 nM) and the affinity ratio prazosin/oxymetazoline (37.4/43.4=0.86) were consistent with an alpha2C selective labelling of [125I]rauwolscine-OHPC. The distribution of [125I]rauwolscine-OHPC binding sites in mouse brain was characterized by autoradiography. The density of binding sites was high in the islands of Calleja, accumbens nucleus, caudate putamen and olfactory tubercles, moderate in the hippocampus, amygdala and anterodorsal nucleus of the thalamus. These findings demonstrated that [125I]rauwolscine-OHPC is a useful radioiodinated probe to label alpha2C adrenoceptors in mouse brain.
    Neurochemistry International 01/2000; 36(1):7-18. · 2.86 Impact Factor
  • Article: Nociceptin receptors in the rat spinal cord during morphine tolerance.
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    ABSTRACT: The anatomical localization of nociceptin receptors was examined by in vitro quantitative autoradiography techniques in rat spinal cord sections by using [(125)I-Tyr(14)]nociceptin. [(125)I-Tyr(14)]nociceptin appeared to interact with a single class of binding sites (K(D)=0.1 nM) present in the grey matter in all laminae of the spinal cord from cervical to sacral levels. Pre-incubation of sections in the presence of 150 mM NaCl, did not modify the radioligand affinity but significantly augmented the number of accessible binding sites and increased specific binding of [(125)I-Tyr(14)]nociceptin differentially on each laminae. In particular, the superficial layers of the dorsal horn exhibited the highest density of sites after pre-wash. Continuous intrathecal infusion of morphine produced a tolerance accompanied by a significant increase in nociceptin site density in the superficial layers. Thus, nociceptin binding sites may have different properties dependent upon the layer and may be up-regulated during the process of opioid-induced tolerance.
    Brain Research 09/1999; 838(1-2):85-94. · 2.73 Impact Factor
  • Article: Synthesis and biodistribution of new oxo and nitrido 99mTc complexes with asymmetrical potentially dianionic or trianionic tetradentate SNNO ligands derived from methyl-2-aminocyclopentene-1-dithiocarboxylic acid.
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    ABSTRACT: In this work, 10 new asymmetrical tetradentate SNNO ligands were prepared by reaction of the amine function of methyl 2-[(beta-aminoethyl)amino]cyclopentene-1-dithiocarboxylate with various bifunctional substituents bearing hydroxyl/ketone and hydroxyl/aldehyde functional groups and with diethyl oxalate. 99mTc labeling efficiency was optimized by adjusting temperature and pH conditions. Seven nitrido and two oxo 99mTc complexes were isolated. Six of them proved to be stable near physiological conditions. Biodistribution studies in the rat showed a significant heart uptake for four of them and strong kidney and liver uptake for the other two.
    Nuclear Medicine and Biology 02/1998; 25(1):65-9. · 3.02 Impact Factor
  • Article: Affinity of neuropeptide FF analogs to opioid receptors in the rat spinal cord.
    C Gouardères, J A Tafani, J M Zajac
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    ABSTRACT: Several high-affinity analogs of neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, NPFF) exhibiting both supraspinal anti-opioid and spinal analgesic activities were studied for their abilities to interact with specific mu, delta, and kappa opioid binding in the rat spinal cord. Measurements by quantitative receptor autoradiography in the superficial layers of the spinal cord revealed that NPFF analogs tested have only a low affinity for opioid receptors since Ki values ranged from 5 to 400 microM. Taking into account the high efficacy of NPFF after intrathecal injection, these results indicate that analgesic effects of NPFF did not result from opioid receptor stimulation.
    Peptides 02/1998; 19(4):727-30. · 2.43 Impact Factor
  • Article: Evaluation of [125I]7 alpha-O-iodoallyl diprenophine as a new potential SPECT opioid receptor imaging agent.
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    ABSTRACT: A new iodinated diprenorphine analog, [125I]7 alpha-O-iodoallyl diprenorphine ([125I]7 alpha-O-IA-DPN), was prepared by iododestannylation and characterized. As an opioid antagonist, this agent showed very high affinity (Ki = 0.4 +/- 0.2 nM) and 63% of specific binding by in vitro and in vivo binding studies. Inhibition curves indicated that this tracer labeled with the same affinities to three opioid receptors (mu = delta = kappa). The findings demonstrate that this proposed compound appears to be potential radioprobe for future study of opioid receptors by in vivo SPECT.
    Nuclear Medicine and Biology 09/1997; 24(6):553-8. · 3.02 Impact Factor
  • Article: Autoradiographic characterization of rat spinal neuropeptide FF receptors by using [125I][D.Tyr1, (NMe)Phe3]NPFF.
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    ABSTRACT: The binding properties of neuropeptide FF (NPFF) receptors were investigated in different laminae of the rat spinal cord by using quantitative autoradiography and [125I][D.Tyr1, (NMe)Phe3]NPFF as radioligand. In the superficial layers, the specific binding of [125I][D.Tyr1, (NMe)Phe3]NPFF was time-dependent, reversible, and saturable (KD = 0.1 nM). Preincubation of spinal sections increased the maximal number of [125I][D.Tyr1, (NMe)Phe3]NPFF binding sites. Bestatin, an inhibitor of aminopeptidases, increased significantly the apparent affinity of NPFF. Optimal binding of [125I][D.Tyr1, (NMe)Phe3]NPFF was observed in the presence of 120 mM NaCl in all laminae of the spinal cord. No significant differences were noted in the salt dependence in laminae I-II, IV-V, and X, and the pharmacological profile of [125I][D.Tyr1, (NMe)Phe3]NPFF binding was similar in each laminae. These results do not support the existence of NPFF receptors subtypes differentially localized in different area of the spinal cord. Our data reveal the effects of tissue treatments on binding characteristics of NPFF receptors and indicate that [125I][D.Tyr1, (NMe)Phe3]NPFF is a useful radioactive probe for the characterization of NPFF receptors in discrete brain areas.
    Brain Research Bulletin 02/1997; 42(3):231-8. · 2.82 Impact Factor
  • Article: Evidence for multiple opioid receptors in the human posterior pituitary.
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    ABSTRACT: The distribution and quantification of opioid receptor types in post-mortem human pituitary cryostat sections was determined by quantitative in vitro receptor autoradiography. Highly specific radioligands were used for each opioid receptor type i.e. [125l]-FK-33-824 for mu-opioid sites, [125l][D.Ala2]-Deltorphin-l for delta-opioid sites and 3H-U69,593 for kappa-opioid sites. None of the five specimens tested exhibited any labeling in the anterior lobe of the pituitary for the three radioligands. As for the posterior pituitary, all 5 specimens contained both mu and kappa-opioid binding sites whereas none of them showed delta-binding sites. The presence of both mu- and kappa-opioid binding sites in the human posterior pituitary contrasts with previous findings in the rat where only kappa-sites have been found. The present study could contribute to understanding of the functional action of opioids in the human pituitary.
    Journal of Neuroendocrinology 12/1996; 8(11):883-7. · 3.14 Impact Factor
  • Article: Technetium labeling of bi, tri and tetradentate ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid: characterization and biodistribution of their oxo and nitrido 99mtechnetium complexes.
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    ABSTRACT: We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid with different donor sets (SN2-, SNO2-, SNN2-, SNNO3- and SNNN3-) and different substituents on the sulfur moieties-SR (with R = H, CH3 or C2H5O(CH3)CH). With five of these ligands technetium nitrido complexes have been obtained with high yields (over 95%) using rather harsh conditions (pH = 1, temperature > or = 80 degrees C), whereas for technetium oxo complexes similar high yields were only obtained with two ligands but with mild conditions (pH = 7-8, temperature approximately equal to 50 degrees C). Changing an OH group for an NH2 has a drastic effect upon labeling yields. The possibility of complexing ligands as either oxo (TcO)3+ or nitrido (TcN)2+ derivatives increases the number of available labeled agents with different overall change and consequently with different biological behavior.
    Nuclear Medicine and Biology 04/1996; 23(3):353-7. · 3.02 Impact Factor
  • Article: Synthesis, characterization and biodistribution of a new technetium-99m complex with trimethylsilylmethylisonitrile. Comparison with 99mTc-TBI and 99mTc-MIBI.
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    ABSTRACT: An isonitrile ligand with a silicium component was synthesized and a copper salt of this ligand was then used to form a 99mTc complex. We evaluated the physicochemical characteristics of the complex and its biodistribution in rat. The chemical properties, i.e. lipophilic affinity and charge, were comparable to those of other 99mTc complexes formed with similar isonitrile compounds (99mTc-MIBI and 99mTc-TBI). In contrast, the tissue biodistribution of this new technetium complex differed markedly, as it was mainly taken up in the liver and not at all in the heart.
    Nuclear Medicine and Biology 08/1995; 22(5):585-8. · 3.02 Impact Factor
  • Article: In vivo binding of [125I]NH2-carfentanil to mu opioid receptors in mouse brain.
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    ABSTRACT: A functionalized derivative of the mu opioid agonist carfentanil was synthesized (NH2-carfentanil) and showed high specific activity when radiolabeled with iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity ratio of over 1200. The ability of [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex vivo binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the mouse was present in the brain. [125I]NH2-carfentanil specific binding was inhibited by co-injection of naloxone or morphine while naltrindole, a delta-selective antagonist, was unable to displace the bound radioligand. Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2-carfentanil specific binding sites, maximal binding occurred in areas with high densities of mu receptors. Peripherally administered iodo-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.
    Nuclear Medicine and Biology 03/1994; 21(2):231-8. · 3.02 Impact Factor
  • Article: Synthesis, characterization and biodistribution of new 99mTc oxo and nitrido complexes with bi- and tetradendate unsaturated NS and N2S2 Schiff bases derived from 2-aminocyclopentene-1-dithiocarboxylic acid as potential heart imaging agents.
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    ABSTRACT: The synthesis, characterization and 99mTc labelling of unsaturated diamino dithiol ligands with methyl dithiocarboxylate functions: 2-aminocyclopentene-1-dithiocarboxylic methyl ester (H2L1), N,N'-ethylene bis(methyl 2-aminocyclopentene-1-dithiocarboxylate) (H2L2) and N,N'-propylene bis (methyl 2-aminocyclopentene-1-dithiocarboxylate) (H2L3) are described. Cationic oxo (Tc = O) and neutral nitrido (Tc = N) complexes were obtained. Biodistribution studies in rat showed a good heart uptake of 99mTcN-L2 (2% ID at 5 min) with a high heart-to-blood ratio (5.8 at 5 min), but this complex also exhibited high lung and liver uptake.
    Nuclear Medicine and Biology 03/1994; 21(2):263-8. · 3.02 Impact Factor
  • Article: Binding in vivo of selective mu and delta opioid agonists: localization by autoradiography.
    M Mokhtari, J A Tafani, J M Zajac
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    ABSTRACT: The in vivo binding properties of cerebral opioid receptors were investigated in mice after intracerebroventricular (i.c.v.) injections of iodinated FK33-824 and [D.Ala2]deltorphin-I which behave in vitro as highly selective ligands possessing high affinity for mu and delta receptors, respectively. [125I]FK33-824 and [125I][D.Ala2] deltorphin-I exhibited similar diffusion kinetics after i.c.v. injection and bound specifically to sites characterized pharmacologically as mu and delta receptors respectively. Autoradiographic analysis revealed that after i.c.v. administration, concentrations of [125I]FK33-824 and [125I][D.Ala2]deltorphin-I remained higher in the circumventricular than in the deep structure of the brain and that specific sites labelled in vivo were differently distributed from those observed after in vitro labelling. FK33-824 was 250 times more analgesic than [D.Ala2]deltorphin-I in the tail-flick test and at doses producing a similar analgesia, [D.Ala2]deltorphin-I occupied a high proportion of mu receptors. Furthermore, analgesic effect of [D.Ala2]deltorphin-I was antagonized by pretreatment with naltrexone but not by naltrindole, a selective antagonist of delta-opioid receptors. These experiments reveal the localization of mu and delta opioid receptors reached after i.c.v. injection and provide evidence to support the suggestion that delta-opioid receptors contribute little or none to the supraspinal antinociception.
    Neuropeptides 10/1993; 25(3):183-91. · 1.55 Impact Factor
  • Article: Synthesis, characterization and biodistribution of new 99mTc Oxo and nitrido complexes of unsaturated tetradentate (N2S2)ligands.
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    ABSTRACT: Three unsaturated Schiff base tetradentate (N2S2 or N2SO) ligands were synthesized and characterized. Oxo and nitrido 99m-technetium complexes were obtained with these ligands. The nitrido complexes were formed using a new easy method available as a kit. When injected into rats and mice, these lipophilic complexes were able to cross the blood-brain barrier but brain perfusion imaging could not be performed due to the insufficient uptake and retention time.
    Nuclear Medicine and Biology 05/1993; 20(3):263-8. · 3.02 Impact Factor
  • Article: Quantitative autoradiographic mapping of delta-opioid receptors in the rat central nervous system using [125I][D.Ala2]deltorphin-I.
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    ABSTRACT: The distribution of delta-opioid binding sites was studied by quantitative autoradiography in rat brain and spinal cord using the highly selective ligand [125I][D.Ala2]deltorphin-I. The binding properties of [125I][D.Ala2]deltorphin-I were investigated by microdensitometry of autoradiographic films with the aid of a computer-assisted image-analysis system. [125I][D.Ala2]deltorphin-I appeared to interact with a single class of sites in all brain areas (KD = 0.9 nM). In 23 regions tested, whatever the delta site concentration, DTLET, a delta agonist, appears to be 2 orders of magnitude more effective than DAGO, a mu agonist, in inhibiting specific [125I][D.Ala2]deltorphin-I binding. The distribution of [125I][D.Ala2]deltorphin-I sites is globally consistent with that of other delta ligands and does not support the existence of a delta-receptor subtype recognized by [D.Ala2]deltorphin-I. [125I][D.Ala2]deltorphin-I binding sites were highly confined, exhibiting selective localization in the neocortex and a diffuse pattern in the striatum, accumbens nucleus, claustrum, layer of bulb, amygdaloid nucleus, pontine nuclei, and inferior colliculus. In several areas a rostro-caudal gradient of site concentration was indicated. [D.Ala2]deltorphin-I binding sites were also present in the substantia gelatinosa at all levels of the spinal cord and, unexpectedly, in deeper laminae and the ventral horn. These results demonstrate the ability of [125I][D.Ala2]deltorphin-I to characterize low concentrations of binding sites and to reveal new localizations of delta receptors.
    Synapse 04/1993; 13(3):231-40. · 2.94 Impact Factor
  • Article: Human brain and spinal cord scan after intracerebroventricular administration of iodine-123 morphine.
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    ABSTRACT: [123I]iodomorphine (IMPH) was administered intracerebroventriculary (i.c.v.) in eight patients treated by i.c.v. morphinotherapy (i.c.v.m.). Scans obtained by gamma-scintigraphy over 1 h post-injection showed only a slight diffusion of IMPH beyond the ventricular system, particular attention being paid to the spinal cord. These data agree well with induced i.c.v.m. analgesia (mean latency 20 min) and biological results such as HPLC assay of morphine in the lumbar cerebrospinal fluid, supporting the action of morphine only on the central opiate receptors.
    International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology 02/1989; 16(5):505-9.
  • Article: [125I][D-Ala2]deltorphin-I: a high affinity, delta-selective opioid receptor ligand.
    S Dupin, J A Tafani, H Mazarguil, J M Zajac
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    ABSTRACT: The selective delta opioid agonist [D-Ala2]deltorphin-I was radioiodinated and the product purified using reverse phase HPLC. The binding characteristics and distribution profile of [125I][D-Ala2]deltorphin-I were assessed in mouse brain using homogenate binding techniques and quantitative autoradiography. [125I][D-Ala2]deltorphin-I bound with high affinity to a single class of sites (KD = 0.5 nM) in brain membrane preparations and striatal sections. Competition studies indicated that [125I][D-Ala2]deltorphin-I was selectively labeling delta opioid receptors as shown by the ratio of apparent affinities for mu and delta receptors (KI mu/KI delta = 1388). The autoradiographical distribution profile of [125I][D-Ala2]deltorphin-I binding sites was also consistent with that of other delta-selective radioligands. The data indicate that [125I][D-Ala2]deltorphin-I binds to delta opioid receptors with high affinity and selectivity. Because of its very high specific activity, it can be detected rapidly with high sensitivity by autoradiographic emulsion.
    Peptides 12(4):825-30. · 2.43 Impact Factor
  • Article: [Prospective survey on adverse effects of radiopharmaceuticals].
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    ABSTRACT: In France, radiopharmaceuticals have been considered as drugs since 1992. Few adverse reactions with radiopharmaceuticals were described in the literature. Some authors have reported a rate of 1 to 6 reactions per 100,000 injections. The purpose of the present study was to evaluate the prevalence of radiopharmaceutical-induced side effects. A prospective survey was performed from November 1993 to May 1995 (during 18 months) in the Department of Nuclear Medicine of the University Hospital in Toulouse. There were 14,794 injections of radiopharmaceuticals (99mTc-phytate, 99mTc-microspheres of serum albumin, 99mTc-dimercapto-succinic acid (DMSA), 99mTc-hydroxymethyldiphosphonate (HMDP), 99Tc-colloid, 99mTc, 99mTc-sestamibi, Thallium-201). Three side effects were reported: one case of necrosis at the injection site, one case of vomiting and one case of dizziness. All the cases occurred with Tc99m-pyrophosphate. According to the WHO definition, the first side effect was classified as 'serious'. The causal relationship was unlikely for the first and second case and probable for the third. The outcome of these side effects was always favorable.
    Thérapie 51(5):550-3. · 0.30 Impact Factor

Institutions

  • 1997–2001
    • IPBS - Institut de Pharmacologie et de Biologie Structurale
      Toulouse, Midi-Pyrenees, France
  • 1993–2001
    • French National Centre for Scientific Research
      Lyon, Rhone-Alpes, France
  • 1997–2000
    • Beijing Medical University
      • Department of Nuclear Medicine
      Beijiang, Zhejiang Sheng, China