Nuclear , Radiopharmaceutical

8/19/2019 Nuclear , Radiopharmaceutical

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A radiopharmaceutical is a radioactive compoundused for the diagnosis and therapeutic treatmentof human diseases.

In nuclear medicine nearly 95% of the

radiopharmaceuticals are used for diagnosticpurposes, while the rest are used for therapeutictreatment.

Radiopharmaceuticals usually have minimal

pharmacologic e¤ect, because in most cases theyare used in tracer uantities.

!herapeutic radiopharmaceuticals can cause tissuedamage by radiation.


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"ecause they are administered tohumans, they should be sterile andpyrogen free, and should undergo alluality control measures reuired of aconventional drug.

A radiopharmaceutical may be aradioactive element such as #$$e, or alabeled compound such as #$#I&iodinatedproteinsand 99m!c&labeled compounds.


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Although the term radiopharmaceutical ismost commonly used, other terms suchas radiotracer, radiodiagnostic agent, and

tracer have been used by various groups.

'e shall use the termradiopharmaceutical throughout,although the term tracer will be usedoccasionally.


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Another point of interest is the deferencebetween radiochemicals andradiopharmaceuticals.

!he former are not usable foradministration to humans due to thepossible lac( of sterility and

nonpyrogenicity.

)n the other hand, radiopharmaceuticalsare sterile and nonpyrogenic and can beadministered safely to humans.


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A radiopharmaceutical has twocomponents*a radionuclide and a pharmaceutical.

!he usefulness of a radiopharmaceuticalis dictated by the characteristics of thesetwo components.

In designing a radiopharmaceutical, apharmaceutical is +rst chosen on thebasis of its preferential localiation in agiven organ or its participation in thephysiologic function of the organ.


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!hen a suitable radionuclide is tagged ontothe chosen pharmaceutical such that afteradministration of the radiopharmaceutical,

radiations emitted from it are detected bya radiation detector.

!hus, the morphologic structure or the

physiologic function of the organ can beassessed. !he pharmaceutical of choiceshould be safe and nonto-ic for humanadministration.


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Radiations from the radionuclide ofchoice should be easily detected by

nuclear instruments,and the radiationdose to the patient should be minimal.


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ince radiopharmaceuticals areadministered to humans, and becausethere are several limitations on the

detection of radiations by currentlyavailable instruments,radiopharmaceuticals should possesssome important characteristics.

!he ideal characteristics forradiopharmaceuticals are*


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1. Easy Availability

!he radiopharmaceutical should be easilyproduced, ine-pensive, and readily availablein any nuclear medicine facility

/omplicated methods of production ofradionuclides or labeled compounds increasethe cost of the radiopharmaceutical.

!he geographic distance between the userand the supplier also limits the availability ofshort&lived radiopharmaceuticals.


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2. Short Efective Hal-Lie

A radionuclide decays with a de+nite half&life, which is called the physical half&life,denoted !p 0or t#123.

!he physical half&life is independent of anyphysicochemical condition and ischaracteristic for a given radionuclide


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2. Short Efective Hal-Lie (cont,..)

Radiopharmaceuticals administered to humansdisappear from the biological system throughfecal or urinary e-cretion, perspiration, or othermechanisms.

!his biologic disappearance of a

radiopharmaceutical follows an e-ponential lawsimilar to that of radionuclide decay.

!hus, every radiopharmaceutical has a biologichalf&life 0!b3.

It is the time needed for half of theradiopharmaceutical to disappear from thebiologic system and therefore is related to adecay constant, 4*9$1!b.


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)bviously, in any biologic system, the loss ofa radiopharmaceutical is due to both thephysical decay of the radionuclide and thebiologic elimination of the

radiopharmaceutical.


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!he net or e¤ective rate 0le3 of the loss ofradioactivity is then related to the physicaldecay constant lp and the biologic decayconstant lb. 6athematically, this is

e-pressed as*

7e 1 7p 8 7b

ince 7 1 4.9$t#2, it follows that

#!e 1 #!p 8 #!bOR

!e 1 0 !p !b3 0 !p 8 !b 3


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:roblem .#

!he physical half&life of ###In is ; hr and the biologic half&life of###In&

used for measurement of the glomerular +ltration rate is #.5 hr.'hat is the

e¤ective half&life of ###In&

Answer

>sing ?. 0.$3,

!e @#*5 ;

; #*5

@

#44*5

*5@ #*B; hr

Radiopharmaceuticals


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. !article E"ission

Radionuclides decaying by a& or b&particleemission should not be used as the label indiagnostic radiopharmaceuticals.

!hese particles cause more radiationdamage to the tissue than do g rays.

Although g&ray emission is preferable, many

b&emitting radionuclides, such as #$#I&iodinated compounds, are often used forclinical studies.


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. !article E"ission (cont,..)

Cowever, alpha emitters should never beused for in vivo diagnostic studies becausethey give a high radiation dose to thepatient.

"ut a and b emitters are useful for therapy,because of the eDective radiation damage toabnormal cells.


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#. $ecay by Electron %a&t're or so"ericransition

"ecause radionuclides emitting particles areless desirable, the diagnostic radionuclidesused should decay by electron capture or

isomeric transition without any internalconversion.

'hatever the mode of decay, for diagnostic

studies the radionuclide must emit a Eradiation with an energy preferably between$4 and $44 (eF. "elow $4 (eF, E rays areabsorbed by tissue


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:hoton interaction in the GaI0!#3 detector usingcollimators. A $4&(eF photon is absorbed by thetissue. AH $44&(eF photon may penetratethrough the collimator septa and stri(e thedetector, or may escape the detector withoutany interaction.

:hotons of $4 to $44 (eF may escape the organof the body, pass through the collimator holes,and interact with the detector.


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#. $ecay by Electron %a&t're or so"eric ransition(cont,..)

and are not detected by the GaI0!l3 detector.

Above $44 (eF, e¤ective collimation of g rays cannotbe achieved with commonly available collimators.

Cowever, recently manufacturers have made

collimators for 5##&(eF photons, which have beenused for planar or :?/! imaging using #


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*. Hi+h ar+et-to-ontar+et Activity Ratio

or any diagnostic study, it is desirable thatthe radiopharmaceutical be localiedpreferentially in the organ under study sincethe activity from nontarget areas can

obscure the structural details of the pictureof the target organ.

!herefore, the target&to&nontarget activity

ratio should be large.


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*. Hi+h ar+et-to-ontar+et Activity Ratio(cont,..)

An ideal radiopharmaceutical should have allthe above characteristics to providema-imum eDcacy in the diagnosis of

diseases and a minimum radiation dose tothe patient.

Cowever, it is diDcult for a given

radiopharmaceutical to meet all thesecriteria and the one of choice is the best ofmany compromises.


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6any radiopharmaceuticals are used for various nuclearmedicine tests.

ome of them meet most of the reuirements for theintended test andtherefore need no replacement.

or e-ample, 99m!cKmethylene diphosphonate 06


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Cowever, there are a number of otherradio pharmaceuticalthat o¤er onlyminimal diagnostic value in nuclear

medicine tests and thus needreplacement.

/ontinual eDort is being made to improveor replace such radiopharmaceuticals.


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*.


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$.


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.


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"ased on these criteria, it is conceivableto design a radiopharmaceutical toevaluate the function andor structure ofan organ of interest.

)nce a radiopharmaceutical isconceptually designed, a de+nite protocol

should be developed based on thephysicochemical properties of the basicingredientsto prepare theradiopharmaceutical.


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!he method of preparation should besimple, easy, and reproducible, and shouldnot alter the desired property of the

labeled compound.

)ptimum conditions of temperature, pC,

ionic strength, and molar ratios should beestablished and maintained for ma-imumeDcacy of the radiopharmaceutical.


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)nce a radiopharmaceutical is developed andsuccessfully formulated, its clinical eDcacy must beevaluated by testing it +rst in animals and then inhumans.

or use in humans, one has to have a Gotice of/laimed Investigational ?-emption for a Gew


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he olloin+ actors nee to beconsiere beore, 'rin+, an aterthe

&re&aration o a neraio&har"ace'tical.


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!he use of compounds labeled with radionuclideshas grown considerably in medical, biochemical,and other related +elds.

In the medical +eld, compounds labeled with β&emitting radionuclides are mainly restricted to invitro e-periments and therapeutic treatment,whereas those labeled with Lemitting

radionuclides have much wider applications.

!he latter are particularly useful for in vivoimaging of di¤erent organs.


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!hese methods and various factorsa¤ecting the labeled compounds arediscussed below.


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In isotope e-change reactions, one or more atoms in amolecule are replaced by isotopes of the same elementhaving di¤erent mass numbers.

ince the radiolabeled and parent molecules areidentical e-cept for the isotope e¤ect, they are e-pectedto have the same biologic and chemical properties.

?-amples are #25I&triiodothyronine 0!$3, #25I&thyro-ine0!B3, and #B/&, $5&, and $C&labeled compounds.

!hese labeling reactions are reversible and are useful forlabeling iodine&containing material with iodineradioisotopes and for labeling many compounds withtritium.


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In this type of labeling, a radionuclide isincorporated into a molecule that has a (nownbiologic role, primarily by the formation of covalentor coordinate covalent bonds. !he tagging

radionuclide is foreign to the molecule and doesnot label it by the e-change of one of its isotopes.

ome e-amples are 99m!c&labeled albumin,99m!c&

In several instances, the in vivo stability of thematerial is uncertain and one should be cautiousabout any alteration in the chemical and biologicproperties of the labeled compound.


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In many compounds of this category, thechemical bond is formed by chelation, thatis, more than one atom donates a pair of

electrons to the foreign acceptor atom,which is usually a transition metal. 6ost ofthe 99m!c&labeled compounds used innuclear medicine are formed by chelation.

or e-ample, 99m!c binds to


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In this approach, a bifunctional chelatingagent is conMugated to a macromolecule0e.g., protein, antibody3 on one side and

to a metal ion 0e.g., !c3 by chelation onthe other side.

?-amples of bifunctional chelating agents

are


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In contrast, in the indirect method, thebifunctional chelating agent is initiallyconMugated with a macromolecule, which

is then allowed to react with a metal ionto form a metal&chelate&macromoleculecomple-. Farious antibodies are labeledby the latter method.

"ecause of the presence of the chelatingagent, the biological properties of thelabeled protein may be altered and mustbe assessed before clinical use.


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Although the prelabeled chelatorapproach provides a purer metalchelatecomple- with a more de+nite structuralinformation, the method involves severalsteps and the labeling yield often is notoptimal, thus favoring the

chelatorantibody approach.


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In biosynthesis, a living organism is grown in aculture medium containing the radioactive tracer,the tracer is incorporated into metabolitesproduced by the metabolic processes of theorganism, and the metabolites are then chemically

separated.

or e-ample, vitamin "#2 is labeled with 4/o or5;/o by adding the tracer to a culture medium inwhich the organism treptomyces griseus isgrown.

)ther e-amples of biosynthesis include #B/&labeled carbohydrates, proteins, and fats.


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Recoil labeling is of limited interest becauseit is not used on a large scale for labeling.

In a nuclear reaction, when particles areemitted from a nucleus, recoil atoms or ionsare produced that can form a bond withother molecules present in the targetmaterial.

!he high energy of the recoil atoms resultsin poor yield and hence a low speci+cactivity of the labeled product.


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everal tritiated compounds can beprepared in the reactor by the Pi0n,α)3

reaction.

!he compound to be labeled is mi-ed witha lithium salt and irradiated in the reactor.

!ritium produced in the above reactionlabels the compound, primarily by theisotope e-change mechanism, and thenthe labeled compound is separated.


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?-citation labeling entails the utiliation of radioactive andhighly reactive daughter ions produced in a nuclear decayprocess.


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• !he maMority of radiopharmaceuticals used inclinical practice are relatively easy to prepare inionic, colloidal, macroaggregated, or chelatedforms, and many can be made using commercially

available (its.

• everal factors that inuence the integrity oflabeled compounds should be (ept in mind.

• !hese factors are described briey below.

E/ciency o the Labelin+ !rocess


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E/ciency o the Labelin+ !rocess

A high labeling yield is alwaysdesirable, although it may not beattainable in many cases.

Cowever, a lower yield issometimes acceptable if theproduct is pure and not damagedby the labeling method, the

e-pense involved is minimal, andno better method of labeling isavailable.

%he"ical Stability o the !ro'ct


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%he"ical Stability o the !ro'ct

tability is related to the type of

bond between the radionuclide andthe compound.

/ompounds with covalent bonds

are relatively stable under variousphysicochemical conditions.

!he stability constant of the labeled

product should be large for greaterstability.

$enat'ration or Alteration


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$enat'ration or Alteration

!he structure andor the biologic

properties of a labeled compoundcan be altered by variousphysicochemical conditions duringa labeling procedure.

or e-ample, proteins aredenatured by heating, at pC below2 and

above #4, and by e-cessiveiodination, and red blood cells aredenatured by heating.

soto&e Efect


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soto&e Efect

!he isotope e¤ect results in di¤erentphysical 0and perhaps biologic3 propertiesdue to diferences in isotope weights.

or e-ample, in tritiated compounds,Catoms are replaced by $C atoms and thediference in mass numbers of $C and C

may alter the property of the labeledcompounds.

It has been found that the physiologicbehavior of tritiated water is di¤erent

from that of normal water in the body.

!he isotope e¤ect is not as serious whenthe isotopes are heavier.

%arrier-0ree or o-%arrier-Ae


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%arrier-0ree or o-%arrier-Ae(%A) State

Radiopharmaceuticals tend to beadsorbed on the inner walls of thecontainers if they are in a carrier&

free or G/A state.

!echniues have to be developed in which the labeling yield

is not afected by the lowconcentration of the tracer in acarrier&free or G/A state.

Stora+e %onitions


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Stora+e %onitions

6any labeled compounds are susceptible

to decomposition at higher temperatures. :roteins and labeled dyes are degraded by

heat and therefore should be stored atproper temperaturesS for e-ample,

albumin should be stored underrefrigeration.

Pight may also brea( down some labeledcompounds and these should be stored in

the dar(. !he loss of carrier&free tracers byadsorption on the walls of the containercan be prevented by the use of silicon&coated vials.

S&ecic Activity


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S&ecic Activity

peci+c activity is de+ned as the

activity per gram of the labeledmaterial.

In many instances, high speci+cactivity is reuired in the applications

of radiolabeled compounds andappropriate methods should bedevised to this end.

In others, high speci+c activity can

cause more radiolysis 0see below3 inthe labeled compound and should beavoided.

Raiolysis


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Raiolysis

6any labeled compounds are decomposed by radiationsemitted by the radionuclides present in them.

!his (ind of decomposition is called radiolysis. !he higher the speci+c activity, the greater the e¤ect of

radiolysis.

'hen the chemical bond brea(s down by radiations from itsown molecule, the process is termed TTautoradiolysis.

UU Radiations may also decompose the solvent, producing freeradicals that can brea( down the chemical bond of the labeledcompoundsS this process is indirect radiolysis.

or e-ample, radiations from a labeled molecule candecompose water to produce hydrogen pero-ide or perhydro-ylfree radical, which o-idies another labeled molecule.

!o help prevent indirect radiolysis, the pC of the solvent shouldbe neutral because more reactions of this nature can occur atal(aline or acidic pC.

Raiolysis 0 cont,V3


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Raiolysis 0 cont,V3

!he longer the half&life of the

radionuclide, the more e-tensive isthe radiolysis, and the more energeticthe radiations, the greater is theradiolysis.

In essence, radiolysis introduces anumber of radiochemical impurities inthe sample of labeled material andone should be cautious about theseunwanted products.

!hese factors set the guidelines forthe e-piration date of aradiopharmaceutical.

!'rication an Analysis


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' ca o a a ys s

Radionuclide impurities are radioactivecontaminants arising from the method of

production of radionuclides.

ission is li(ely to produce more impuritiesthan nuclear reactions in a cyclotron orreactor because +ssion of the heavy nuclei

produces many product nuclides. !arget impurities also add to the

radionuclidic contaminants.

!he removal of radioactive contaminantscan be accomplished by various chemicalseparation methods, usually at theradionuclide production stage.

!'rication an Analysis 0cont 3


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!'rication an Analysis 0cont,..3

Radiochemical and chemical

impurities arise from incompletelabeling of compounds and can beestimated by various analyticalmethods such as solvent e-traction,

ion e-change, paper, gel, or thin&layer chromatography, andelectrophoresis.

)ften these impurities arise afterlabeling from natural degradationas well as from radiolysis.

Shel Lie


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Shel Lie A labeled compound has a shelf life during

which it can be used safely for its intendedpurpose.

!he loss of eWcacy of a labeled compound overa period of time may result from radiolysis anddepends on the physical half&life of theradionuclide, the solvent, any additive, thelabeled molecule, the nature of emitted

radiations, and the nature of the chemical bondbetween the radionuclide and the molecule.

>sually a period of three physical half&lives or ama-imum of months is suggested as the limitfor the shelf life of a labeled compound.

!he shelf&life of 99m!c&labeled compoundsvaries between 4.5 and # hr, the mostcommon value being hr.


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n n'clear "eicine, the to "ost re'ently'se raion'clies are 33"c an 11.

he 33"c-labele co"&o'ns constit'te

"ore than 456 o all raio&har"ace'ticals'se in n'clear "eicine, hereas 12- an11labele co"&o'ns an other n'cliesacco'nt or the rest.

he &rinci&les o ioination an 33"c-labelin+ are isc'sse belo.


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Iodination is used e-tensively for labelingthe compounds of medical and biologicalinterest. Iodine is a metallic elementbelonging to the halogen group FIIA.

Its atomic number is 5$ and its only stableisotope is #2;I.

!he isotope #25I is commonly used forproducing radiolabeled antigens and othercompounds for in vitro procedures and hasthe advantage of a long half&life 04 days3.


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Cowever, its low&energy 02;& to $5& (eF3photons ma(e it unsuitable for in vivoimaging.

!he isotope #$#I has an &day half&lifeand $B&(eF photons and is used forthyroid upta(e and scan.

Cowever, its b emission gives a largerradiation dose to the patient than #2$I,and it is e-clusively used for thyroidtreatment.


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Iodination of a molecule is governedprimarily by the o-idation state of iodine.

In the o-idied form, iodine bindsstrongly to various molecules, whereas inthe reduced form, it does not.

/ommonly available iodide is o-idied toI by various o-idiing agents.


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!he free molecular iodine has the structure of IKIin aueous solution.

In either case the electrophilic species I does note-ist as a free species, but forms comple-es withnucleophilic entities such as water or pyridine.


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!he hydrated iodonium ion, C2)I and hypoiodousacid, C)I, are believed to be the iodinating speciesin the iodination process.

Iodination occurs by electrophilic substitution of ahydrogen ion by an iodonium ion in the molecule ofinterest, or by nucleophilic substitution 0isotopee-change3 where a radioactive iodine atom ise-changed with a stable iodine atom that is alreadypresent in the molecule.

!hese reactions are represented as follows*

Gucleophilic substitution*


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?lectrophilic substitution*


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In protein iodination, the phenolic ring of tyrosine is theprimary site of iodination and the ne-t important site is theimidaole ring of histidine.

!he pC plays an important role in protein iodination. !heoptimum pC is ; to 9.

!emperature and duration of iodination depend on the type ofmolecule to be iodinated and the method of iodination used.

!he degree of iodination a¤ects the integrity of a protein

molecule and generally depends on the type of protein andthe iodination method.

Gormally, one atom of iodine perprotein molecule is desirable.


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!here are several methods of iodination, andprinciples of only the important ones are describedbelow.


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!he triiodide method essentially consists ofadding radioiodine to the compound to belabeled in the presence of a mi-ture ofiodine and potassium iodide*


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where RC is an organic compound beinglabeled.

In the case of protein labeling by thismethod, minimum denaturation of proteinsoccurs, but the yield is low, usually about#4% to $4%.

"ecause cold iodine is present, the speci+cactivity of the labeled product isconsiderably diminished.


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/hloramine&! is a sodium salt of G&monochloro&p&toluenesulfonamide and is a mild o-idiing agent.

In this method of iodination, +rst the compound for

labeling and then chloramine&! are added to asolution of #$#I&sodium iodide.

/hloramine&! o-idies iodide to a reactive iodinespecies, which then labels the compound.

ince cold iodine need not be introduced, highspeci+c activity compounds can be obtained bythis method and the labeling eX& ciency can bevery high 0Y94%3.


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Cowever, chloramine&! is a highly reactivesubstance and can cause denaturation of

proteins.

ometimes milder o-idants such assodium nitrite and sodium hypochloritecan be used in lieu of chloramine&!.

!his method is used in iodination ofvarious compounds.


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6any proteins can be radioiodinated bythe electrolytic method, which consists ofthe electrolysis of a mi-ture of radioiodide

and the material to be labeled.

In the electrolytic cell, the anode andcathode compartments are separated by

a dialying bag that contains the cathodeimmersed in saline, whereas the anodecompartment contains the electrolyticmi-ture.


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In enymatic iodination, enymes, such aslactopero-idase and chloropero-idase, and nanomolaruantities of C2)2 are added to the iodination mi-turecontaining radioiodine and the compound to be labeled.

!he hydrogen pero-ide o-idies iodide to form reactiveiodine, which in turn iodinates the compound.


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In the conMugation method, initially G&succinimidyl&$0B&hydro-yphenyl3& propionate 0G&C::3 is radioiodinated bythe chloramine&! method and separated from thereaction mi-ture.

!he radioiodinated G&C:: in dry benene is availablecommercially.

:roteins are labeled by this agent by allowing it to reactwith the protein molecule, resulting in an amide bondwith lysine groups of the protein.

!he labeling yield is not very high, but the method allowsiodination without alteration of protein molecules whosetyrosine moieties are susceptible to alteration, althoughin vivo dehalogenation is encountered in some instances.


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!o improve the in vivo stability of iodinated proteins,various organometallic intermediates such asorganothallium, organomercury, organosilane,organoborane, and organostannane have been usedto iodinate the aromatic ring of the precursor.

!he carbon&metal bond is cleaved by radioiodinationin the presence of o-idiing agents such aschloramine&! and iodogen.

)f all these, organostannane Zsuccinimidyl para&tri&n&butylstannyl benoate 0""3[ is most attractivebecause of the ease of preparation, stability, andeasy e-change reaction with radioiodine.


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:roteins and cell membranes can beradioiodinated by the iodogen method.

Iodogen or chloramide 0#, $, B, &tetrachloro&$a, a&dip solved in methylenechloride is evaporated in tubes in order toobtain a uniform +lm coating inside thetube.

!he radioidide and protein are mi-edtogether in the tube for #4 to #5 min, andthe mi-ture is removed by decantation.


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Iodogen o-idies iodide, and iodine then labels theprotein.

!he unreacted iodide is separated by columnchromatography of the mi-ture using ephade- gelor


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In the iodo&bead method, iodo&beads are used toiodinate various peptides and proteins containing atyrosine moiety.

Iodo&beads consist of the o-idant G&chlorobenenesulfonamide immobilied on 2.&mmdiameter nonporous polystyrene spheres. !hesespheres are stable for at least months if stored inan amber bottle at B /.

Radioiodination is carried out by simply adding +veto si- iodo&beads to a mi-ture of protein 0\#44 mg3and #$#I&sodium iodide in 4.5 ml of phosphatebu¤er solution contained in a capped polystyrenetube.


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!he reaction is allowed to proceed for #5 min atroom temperature.

!he iodination mi-ture can be removed bypipetting and iodinated protein is then separatedby conventional techniues.

!his method has been claimed to be very

successful with little denaturation of the protein.

!he labeling yield is almost 99%.


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After radioiodination the residual freeiodide is removed by precipitation, anione-change, gel +ltration, or dialysisS the

particular method of choice depends onthe iodinated compound.

6any iodinated compounds can be

sterilied by autoclaving, but steriliationof labeled proteins must be carried out bymembrane +ltration because autoclavingdenatures proteins.


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In general, iodine binds +rmly and irreversibly toaromatic compounds, but its binding to aliphaticcompounds is rather reversible.

Iodine binds with amino and sulfhydryl groups, butthese reactions are reversible.

:artially unsaturated aliphatic fatty acids andneutral fats 0e.g., oleic acid and triolein3 can be

labeled with radioiodine.

Cowever, iodination saturates the double bond inthese molecules and thus alters their chemical andperhaps biological properties.


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Farious e-amples of radioiodinated compounds are#25I&, or #$#I&labeled human serum albumin, +brinogen,insulin, globulin, and many hormones, antibodies andenymes.

!he maMor drawbac( of #$#I&labeled compounds is thehigh radiation dose to the patient and high&energyphotons 0$B (eF3.

!he radiation characteristics of #2$I are suitable for usein vivo, and with their increasing availability many #2$I&radiopharmaceuticals are prepared for clinical use innuclear medicine.

In many institutions, #2$I&sodium iodide is usedroutinely for thyroid studies.


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As previously mentioned, more than 4% ofradiopharmaceuticals used in nuclear medicine are 99m!c&labeled compounds.

!he reason for such a preeminent position of 99m!c in clinicaluse is its favorable physical and radiation characteristics.

!he &hr physical half&life and the little amount of electronemission permit the administration of millicurie amounts of99m!c radioactivity without signi+cant radiation dose to thepatient. In addition, the monochromatic #B4&(eF photons arereadily collimated to give images of superior spatial resolution.

urthermore, 99m!c is readily available in a sterile, pyrogen&free, and carrier&free state from 996oK99m!c generators.


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Nuclear , Radiopharmaceutical