RADIOIONIDATION REACTIONS FOR RADIO PHARMACEUTICALS

111 Pages·2006·2.092 MB·English

by  HEINZ H. COENEN, JOHN MERTENS, BERNARD MAZIEÈRE (eds.)

RADIOIONIDATION REACTIONS
FORRADIOPHARMACEUTICALS
RADIOIONIDATION
REACTIONS FOR
RADIOPHARMACEUTICALS
Compendium for Effective Synthesis Strategies
by
HEINZ H. COENEN
InstituteofNuclearChemistry,ResearchCentreJu¨lich(FZJ),
Ju¨lich
JOHN MERTENS
BEFY/NUGE–RadiopharmaceuticalChemistry,
Bruxelles
and
BERNARD MAZIE`RE
CEA/DRIPP–De´partementdeBiologieServiceHospitalier
Frederic-Joliot,Orsay
withcontributions from
Peter Bla¨uenstein, Patrik Emond, Yves Frangin,
Denis Guilloteau,Marielle Gysemans, Marcus Holschbach,
ChristianLoc’h,August P.Schubiger and Syed M. Qaim
HeinzH.Coenen JohnMertens
InstituteofNuclearChemistry, BEFY/NUGE–Radiopharmaceutical
ResearchCentreJu¨lich(FZJ), Chemistry,
Ju¨lich,Germany Brussels,Belgium
BernardMazie`re
CEA/DRIPP,
De´partementdeBiologieServiceHospitalierFrederic-Joliot,
Orsay,France
AC.I.PCataloguerecordforthisbookisavailablefromtheLibraryofCongress.
ISBN-10 1-4020-4560-3(HB)
ISBN-13 978-1-4020-4560-8(HB)
ISBN-10 1-4020-4561-1(e-book)
ISBN-13 978-1-4020-4561-5(e-book)
PublishedbySpringer,
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(cid:1)2006Springer
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PREFACE
Foundedin1971,COSTisanintergovernmentalframeworkforEuropean
Cooperation in the field of scientific and technical research, allowing the
coordination of nationally funded research on a European level. COST
actionscoverbasicandprecompetitiveresearch,aswellasactivitiesofpublic
utility.ThegoalofCOSTistoensurethat Europeholdsastrongpositionin
thefieldofscientificandtechnicalresearchforpeacefulpurposes,byincreas-
ing European cooperation and interaction.
COSTconsistsinactions,thedurationofwhichisgenerally4years.Two
actions,COSTB3entitled‘‘DevelopmentofNewRadiotracersandMethods
of Quality Assurance for Nuclear Medicine Applications’’ and COST B12
entitled ‘‘Radiotracers for In Vivo Assessment of Biological Functions’’,
which have been devoted to radiopharmaceutical chemistry and radiophar-
maceuticalvalidation, weresuccessfullycompleted.
Radiochemicalmethodologyconstitutesthemostimportantbaseforsuc-
cessful in vivo functional imaging in nuclear medicine. For single-photon
emission tomography (SPET) imaging, radioiodination methodology allows
the development of potent radiotracers, and several of them are presently in
clinicalroutine.
Many previous publications have tackled the specific problems of radio-
iodination,butthetimeforastate-of-the-artbookseemedrightnowsincethis
fieldhasadvancedoverthelast30yearstoreachalevelwhereguidelinesand
expert systems can be suggestedfor the main methodological aspects.
vi Preface
This book has emerged from an original idea during the course of COST
ActionB3andwasdevelopedduringthecourseofCOSTActionB12withthe
helpofmanyrecognisedEuropeanexpertsinthefield.Sincerethankstoallof
them for their very precious support, advice and contributions.
TheauthorsgratefullyacknowledgethesupportofCOST,which,allalong
the duration of the actions, has encouraged the preparation and the finalisa-
tion of a collectivetextbook.
Heinz H. Coenen
John Mertens
Bernard Mazie`re
CONTRIBUTORS
Peter Bla¨uenstein Center for Radiopharmaceutical Science, Paul-Scherrer-
Institut (PSI), CH-5232 Villigen
Heinz H. Coenen Institute of Nuclear Chemistry, Research Centre Ju¨lich
(FZJ), D-52425 Ju¨lich
Patrik Emond Centre Hospitalier Re´gional et Universitaire, Universite´
Franc¸ois Rabelais, Laboratoire de Biophysique Me´dicale et Pharmacie CHU
BretonneauINSERM U316, 31, Av Monge, F-37200 Tours
YvesFranginCentreHospitalierRe´gionaletUniversitaire,Universite´ Fran-
c¸ois Rabelais, Laboratoire de Biophysique Me´dicale et Pharmacie CHU Bre-
tonneau INSERM U316, 31, Av Monge, F-37200 Tours
Denis Guilloteau Centre Hospitalier Re´gional et Universitaire, Universite´
Franc¸ois Rabelais, Laboratoire de Biophysique Me´dicale et Pharmacie CHU
BretonneauINSERM U316, 31, Av Monge, F-37200 Tours
Marielle Gysemans Belgian Nuclear Research Center (SCK-CEN), Boer-
etang 200,B-2400Mol
MarcusHolschbachInstituteofNuclearChemistry,ResearchCentreJu¨lich
(FZJ), D-52425 Ju¨lich
ChristianLoc’hCEA/DRIPP,De´partementdeBiologieServiceHospitalier
Frederic-Joliot, 4,place duGe´ne´ral Leclerc, F-91406 Orsay
Bernard Mazie`re CEA/DRIPP, De´partement de Biologie Service Hospita-
lier Frederic-Joliot, 4,place duGe´ne´ral Leclerc, F-91406 Orsay
John Mertens BEFY/NUGE – Radiopharmaceutical Chemistry, Laarbeek-
laan 103,B-1090Brussels
Syed M. Qaim Institute of Nuclear Chemistry, Research Centre Ju¨lich
(FZJ), D-52425 Ju¨lich
August P. Schubiger Center for Radiopharmaceutical Science, Paul-Scher-
rer-Institut(PSI),CH-5232 Villigen
RADIOIODINATION COMPENDIUM
Summary
Several of the around 30 radioisotopes of iodine find wide application in
life sciences research both invitro and invivo.
Most nuclear medicine departments possess one or more imaging devices
forsingle-photonemissiontomography(SPET).Moleculesofbiologicalinter-
est, especially for functional imaging of metabolism and neurotransmission
functionsusingSPET,areoftenlabelledwith123I.Inthishandbook,themajor
production routes of the six most relevant radioiodine isotopes are reviewed
andvariousmethodsforlabellingmoleculesofbiologicalinterestwithradio-
iodinearedescribed,includingtheirbasicreactionmechanisms.Theinfluence
of iodine introduction on physico-chemical, pharmaceutical and pharmaco-
logical properties of radiopharmaceuticals are discussed and corresponding
examplesofradioiodinatedpharmaceuticalpreparationsaregiven.Finally,an
expertsystemprovidingguidelinesforchoosingthemostappropriatemethod
of radioiodination according to the chemical structure of the molecule of
interestfortraceruseisproposed.
TABLE OF CONTENTS
1 Introduction..................................................................... 1
1.1 Authentic Labelling.........................................................................2
1.2 LabellingwithMetallic Radioisotopes............................................2
1.3 LabellingMethods for Radioiodine................................................2
2 Iodine Radionuclides........................................................ 5
2.1 Physical Properties and Areasof Application.................................5
2.2 Radiochemical and Radionuclidic Purity........................................5
2.3 Specific Radioactivity......................................................................7
2.4 Production of Iodine Radionuclides................................................8
2.4.1 Production of 120I..................................................................8
2.4.2 Production of 122I..................................................................9
2.4.3 Production of 123I..................................................................9
2.4.4 Production of 124I................................................................12
2.4.5 Production of 125I................................................................13
2.4.6 Production of 131I................................................................14
2.5 References.....................................................................................15
3 Iodinated Radiopharmaceuticals .....................................17
3.1 Physico-chemicalProperties..........................................................17
3.1.1 Carbon–iodine bond............................................................17
3.1.2 Lipophilicity.........................................................................20
3.2 Pharmaceutical Properties.............................................................23
3.2.1 Chemical and Radiochemical Purity....................................23
3.2.2 StabilityIn Vitro and Shelf-life............................................24
x Table ofContents
3.2.3 Pharmacological Characteristics..........................................25
3.2.4 Pharmaceutical Considerations............................................26
3.3 References......................................................................................26
4 Methods of Radioiodination............................................29
4.1 NucleophilicSubstitution..............................................................30
4.1.1 General.................................................................................30
4.1.2 Halogen Exchange inAliphatic Compounds.......................30
4.1.3 Halogen Exchange inAromatic Compounds.......................32
4.1.4 Copper-assisted Halogen Exchange.....................................34
4.1.5 Radioiodo-dediazonisation..................................................37
4.1.6 References............................................................................38
4.2 Electrophilic Substitution..............................................................45
4.2.1 General Considerations........................................................45
4.2.2 Oxidising Reagents...............................................................46
4.2.3 DirectElectrophilic Radioiodination
(Radioiodo-deprotonation)..................................................50
4.2.4 Demetallation Techniques
(Radioiodo-demetallation)...................................................51
4.2.5 References............................................................................57
4.3 Macromolecule Labelling..............................................................62
4.3.1 Protein Radioiodination......................................................62
4.3.2 Oligonucleotide Radioiodination.........................................68
4.3.3 References............................................................................69
5 Iodinated Radiopharmaceuticals......................................73
5.1 Examples of Nucleophilic Labelling..............................................73
5.1.1 Interhalogen Exchange.........................................................73
5.1.2 OtherMethods.....................................................................76
5.2 Examples of Electrophilic Labelling..............................................77
5.2.1 DirectIodination.................................................................77
5.2.2 Radioiodo-demetallation.....................................................80
5.3 References......................................................................................84
6 Expert System................................................................87
6.1 General Considerations.................................................................87
6.2 Activating Effects ofAromatic Substituents.................................88
6.2.1 Aromatic Nucleophilic Substitution(SN ).........................88
Ar
6.2.2 Aromatic Electrophilic Substitution (SE ).........................89
Ar