Radiopharmaceuticals

Radio pharmaceuticals, Pharmaceutical Inorganic Chemistry

1. 1
Esha Bhavin Shah
Assistant Professor
Department of Pharmaceutical Chemistry and
Quality Assurance
Babaria Institute of Pharmacy
Bits Edu Campus
Email: [email protected]

2. 1.Writeashortnoteonradiopharmaceuticals/Whatareradiopharmaceuticals?
Enumerateunitsofradioactivity.
2.Propertiesofalpha,betaandgammarays/Noteonbehaviouralpropertiesof
differentradiations.
3.Definehalflife,radioisotopes.
4.Giveanaccountofclinicalapplicationsofradiopharmaceuticals/Applicationsof
radiopharmaceuticalsinmedicine.Giveabriefaccountonthetherapeuticand
diagnosticapplicationsofinorganicradiopharmaceuticals.
5.Giveanaccountofprecautionstobetakenwhilehandlingandstorageof
radiopharmaceuticalsornoteonhandlingandstorageofradioactivematerials.
6.DiscussaboutmeasurementofradioactivityorS.NonGMcounter.Explain
workingofGMcounterorNoteonscintillationcounter.WriteanoteonGM
counter.Givepreparation,propertiesandusesofBariumsulphate.
7.GiveusesofSodiumiodide[131],Iron[59Fe],Cyanocobalamine[57Co]/study
ofsodiumiodideasradioisotope.
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GTU imp questions

3. WHAT ARE RADIOACTIVE SUBSTANCES???? ( GTU imp)
Radioactivesubstanceshaveapropertyofemittingraysor
particleswhichaffectthephotographicplate.Forty
radioactiveelementsareknownwhicharearrangedas
Uraniumseries,ThoriumseriesandActiniumseries.
Theelementsareknownasradioactivebecausetheyare
unstableandundergodecompositionalongwithemissionof
radiationsorrays.
Theradiationsorrayswhichareemittedarefollowing:
Alpharays
Betarays
Gammarays
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Anynucleotidewhichisnotradioactivein
natureisregardedasstable.Tobestable,a
nuclidemaypossessappropriateenergy.
Thosenuclideswhichundergospontaneous
nuclearchangesoastoattainstabilityby
emittingradiationsarecalledas
radionuclidesorradioisotopes.

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6. Alpharays
Theseraysorparticleshavelowpenetratingpower.
Theyhavepositivechargeandcanbedetectedbyastrongmagneticfield.
Theycarrytwopositivecharge.
Theyhaveamassof4amu(atomicmassunit)
Heavymetalshavecapacitytoemitsuchtypeofrays.
Allalphaparticlesarehavingthesameenergy.
Thepenetratingpowerofalpharaysislessascomparedtootheremissions.
Becauseoflowpenetratingpowerofalphaparticles,elementswhichemit
alpharaysdonotfinduseinbiologicalapplicationsbecausetheycannot
penetratetissue.

226
88Ra---------------------------
222
86Rn+
4
2He
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7. Beta Rays:
Thesehave2types:
1.Electricallypositivelychargedparticleswhicharecalled‘positrons’
2.Electricallynegativelychargedparticleswhicharecalled‘Negatrons’
Theyhavegreaterpenetratingpowerthanthatofalpharays.
Betaparticleshavenegligiblemass.
Theseparticlesareusuallyaccompaniedbygammaradiation.Betaparticleshaveless
ionizingpowerthanalphaparticles.
Gammarays:
Thesehavebeenmorepenetratingthanalphaandbetarays.
Theyarehavingthesamecharacterasthatofveryshortelectromagneticwavescalled
X-rays.
Theyhavenomassorcharge.
Gammaraysareproducedduringdisintegrationofradioactivesubstancesalongwith
betaradiationandduringnuclearfission.
Theyareunchargedandhavepoorionizingpower.
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8. Type of
radiation
emitted &
symbol
Nature of the
radiation
formation, structure,
relative mass, electric
charge
Penetratingpower(and
speed),andwhatwillblock
it(moredensematerial,
moreradiationisabsorbed
BUTsmallermassor
chargeofparticle,more
penetrating)
Ionisingpower-the
abilityto remove
electronsfromatomsto
formpositiveions,the
processiscalledionisation
Alpha
particle
radiation
a helium nucleus of 2
protons and 2
neutrons, mass = 4,
charge = +2, is
expelled at high
speed from the
nucleus
Lowpenetration,slowest
speed,biggestmassand
charge,stoppedbyafewcm
ofairorthinsheetofpaper
Veryhighionisingpower,
thebiggestmassandcharge
ofthethreeradiation's,the
biggest'punch'inripping
offelectronsfrom
molecules,otherionsare
formed
Beta
particle
high kinetic energy
electrons
Moderate penetration Moderate ionizingpower
Gamma Veryhighfrequency
electromagnetic
radiation
mass=0,charge=0,
gamma emission
oftenaccompanies
betadecay
Very highly penetratingThe lowest ionising power

9. Esha Shah 9
What are isotopes??

10. Types of Radionucleotides
1)Natural radionucleotides:
They include about 40 high atomic weight elements such as Uranium 238,
Radium 226, which may be alpha, beta, or gamma emitters and also some
moderate weight elements such as Potassium 40, Rubidium 87.
2) Artificial Radionucleotides
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11. Esha Shah 11
What are radiopharmaceuticals? Enumerate units of radioactivity.
Units of radioactivity
1.Curie(c):Definedasquantityofanyradioactivesubstancewhichundergoesthe
samenumberofdisintegrationsinunittimeasof1gofradiumandisequalto
3.7x10
10
disintegrationspersecond.
2.Roentgen: it is the unit of exposure 1R= 2.58 x 10
-4
coulomb kg
-1
3.RAD: it is the unit of absorbed dose. Pharmaceutical dosage forms are described
in RAD units.
4.REM: I t is unit of dose equivalent.
5.Exposure rate constant
6.RBE (Relative biological effectiveness): shows effect of radiation, alpha, beta and
gamma on the biological system.

12. Production of Radioisotopes:
Theyareproducedas:
1)Reactorirradiation:Reactorishavinganarrangementoffissionablematerialina
moderator,whichslowsdownthefastneutronstothermalenergies.Thefissionablematerial
likeuraniumistakenintheformofrodswhicharearrangedinalatticepatternandhencethe
neutronfluxismaximuminthecentrewherethereismosturanium.Aheavywatermoderated
reactorusingenricheduraniumishavingamaximumfluxof10
14
neutronscm
-2
s
-1
2)Cyclotronirradiation:Whilethereactorsareabletoproduceafluxofneutronsand
gammarays,acceleratingmechanismscanusemanyothertypesofbombardingparticles
whichhavebeenchargedparticles.Theycanbeacceleratedtohighvelocitiessoasto
overcometherepulsiveforcesofthenucleus.Thebeamofenergeticparticleshasbeensmall
andtargetsforirradiationhavetobeputinthisbeam.Thenumberofsamplesthatcanbe
irradiatedatatimehasbeenlimitedandtheyieldshasbeenlow.Butontheotherhandmany
isotopeswhichotherwisecannotbeproducedinareactorcouldbeproducedinacyclotron.
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13. Q: Note on handling and storage of radiopharmaceuticals
(GTU Imp.)
Greatcareneedstobetakeninhandlingandstorageofradioactivematerialsfor
protectingpeopleandpersonnelwhohandleit,fromtheharmfulradiationtheyemit.
Certainprecautionshavetobetakenwhileworkingwithdetectors,tracerequipment,
radioassaymanufacturingorhandlingofradioactivematerials.
Inordertohaveprotectionfromhazardsofradiation,radioactivematerialsmustbe
storedinanareanotfrequentlyvisitedbypeople.
Shieldingmayberequired.
ThickglassorPerspexcontainersprovidesufficientshielding.
Toprotectfromgammarays(highpenetrationpower),leadshieldinghastobeused.
Thestorageareamustberegularlycheckedforradioactivity.
RADIOACTIVELIQUIDS.
Workingareashouldnotgetcontaminatedwithradioactivematerial.
Ifradioactiveliquidistobehandled,itmustbecarriedintrayswithabsorbent
tissuepaper,sothatanyspillagewillgetabsorbedbythepaper.

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Rubbergloveshavetobeusedwhenworkingwithradioactiveliquids.
Pipettesoperatedbymouthshouldneverbeused.
Wasteofradioactivematerialhastobestoredtillitsactivitybecomeslowandthen
onlyitshouldbedisposed.
PRECAUTIONS Whilehandlingandstorageofradioactivesubstances:
1.Oneshouldnottouchtheradioactiveemitterwithhandbutitshouldbehandledby
meansofforceps.
2.Smoking,eatinganddrinkingactivitiesshouldnotbehandledinlaboratorywhere
radioactivematerialishandled.
3.Sufficientprotectiveclothingandshieldinghavetobeusedwhilehandlingof
materials.
4.Radioactivematerialshavetobestoredinsuitablelabelledcontainers,covered
(shieldedbyleadbricks)andpreferablyinaremotecorner.
5.Areaswhereradioactivematerialsarestoredshouldbemonitoredandtestedfor
radioactivityregularly.
6.Disposalofradioactivematerialsshouldbecarriedoutwithgreatcare.

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StrictrequirementsareprescribedbythedepartmentofAtomicenergy(DAE)forthe
establishmentofaradioactivefacilityinthehospitalorpharmacy.
Theseincludespecificationsforpremises,storagespace,workingarea,disposal
protocol,trainingofpersonnel,periodiccheckoncontaminationorleakage.

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Give uses of Sodium iodide I-131
Used as a diagnostic aid for studying the functioning of the thyroid gland.
Used in scanning the thyroid for determining the size, position and possible tumour
location.
Used in the treatment of severe cardiac disease (Sodium iodide I-131), which
reduces work load on heart.
Radioactive iodine in thyroid carcinoma (cancer): The isotope is used most
frequently after the surgical removal of cancer to treat any residual tumour
tissues.

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Iron 59:
Iron59isabetaandgammaemittingisotope.
Usedindiagnosistostudytheironmetabolismandtostudytheredbloodcell
formation.
Thepreparationisadministeredorallyforstudyingtheabsorptionofiron
fromGIT.
AdministeredI.Vtostudyincorporationofironinformationofredblood
cells.
Usedtostudytheformationanddestructionofspleen,liveretc.fromoutside
thebody.

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Applications of Radioisotopes:( GTU imp)
Theyfinduseinmedicinein4differentways:
1.RadioisotopesinTherapy(Emittedradiationsusedtodestroycellsincondition
likecancer)
2.RadioisotopesinDiagnosis(Radioactivetracers)
3.Research(Biologicalandmedicinalstudiesbyuseofradioactiveisotopesas
tracers)
4.Sterilization (For sterilization of pharmaceuticals and surgical instruments)

19. Applications:
Diagnosticapplications:RadiopharmaceuticalsaredevelopedbasedontheADME(absorption,
distribution,metabolism,excretion)propertiesofthebody.Byadministeringa
radiopharmaceuticaltoapatient,imagesofthetargetedsitecanbeproducedbyagammacamera.
Theimagescanthenbeanalyzedbythenuclearmedicinedoctortodetectanymedicalproblems.
Radiopharmaceuticalsaremostwidelyusedtodetectvariousformsofcancer.Dependingonthe
sitefordiagnosisthereisaspecifiedrouteofadministration.
TherapeuticuseofRadiopharmaceuticals:Radioactivitycanbeusedinmedicineand
pharmacyindifferentareas,thefirstbeingradiology,inwhichanexternalsourceofradioactivity
passesthroughapatientandradiationisabsorbedbymoredensetissuesandnotbylessdense
tissuesandanimageisultimatelyformed.Thesecondisradiationtherapy,whichtreatsfortumors
usinganexternalsourceofradiationtotryandablateatumor.Thisrequireslotsofradiationin
veryhighdoses.Nuclearmedicineusesaninternalsourceofradiationtobedetectedexternally,
unlikethetwopreviouslymentioned.Apatientisinjectedwitharadiopharmaceutical,whichhasa
radioactivecomponentthatdecaysandapharmaceuticalcomponentwhichtakesitadesired
organ.
Radiopharmaceuticalscanbeusedtodestroymalfunctioningcells.Thismethodoftherapyis
calledradiotherapy.Itcanbeusedforbothbenignandmalignantcancers.Inordertodestroythe
diseasedtissue,aradionuclidehastoemitbeta,alpha,orlowenergyconversionelectronemitters.
Betaradiationiseffectiveforlargetumorsandalpharadiationiseffectiveforsmallertumors.
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20. I) In therapeutics:
Thetherapeuticallyusedradioisotopeshavebeenfoundtodependmainlyon
theirabilitytoionizeatoms.
Theenergymeasurementinvolvedinradiationandresultinginionizationmay
beexpressedinmillionsofelectronvoltscalledMeV.
Thestrengthofalpha,betaandgammaraysinexpressedinMeV.
Allradiationsbringaboutionizationofatomsintheirpaths.
Theradiationofshortwavelength(gammarays)ishavinghighpenetrating
powerthanlongwavelength(betarays).
ThegreatertheMeVoftherays,themoredestructiveitbecomestothe
surroundingtissues.
RADIOPHARMACEUTICALS CANDESTROYMALFUNCTIONING
CELLS.
Thismethodoftherapyiscalledradiotherapy.Itcanbeusedforbothbenign
andmalignantcancers.
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21. Examples:
Gold(
198
Au)isusedintreatmentofabdominalandpleuraleffusionsassociated
withmalignanttumours.Itisgivenintheformofcolloidalgoldsuspension.
Gold(
198
Au)alsousedintreatmentofcarcinomaofuterusandurinarybladder.
Cobaltlabelledcyanocobalamine(vitaminB12)isusedindiagnosisof
perniciousanaemia.
Sodiumiodidepreparationfindsuseintreatmentofthyroiddisorders.
Calciumisusedtostudybonestructureandincarcinomaofbone.
Strontium90isusedindiagnosisofsuperficialcarcinomas.
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22. Radioisotopesmaybeusedinternallyorexternally.
Iftheradioisotopeareusedexternallyorusedasimplantsinsealedcapsuleinatissue,
thedosecouldbeterminatedbyremovalorsources.
Iftheyaregiveninternally,asunsealedsources,thedosecannotbestoppedbythe
removalofthesource.
Thetotaldoseintherapeuticapplicationsmaybecalculatedonthebasisofeffective
halflifeoftheisotope,concentrationoftheisotopeandthetypeandenergyofthe
radiationemitted.
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23. In diagnosis:
Radioactivetracersfinduseinmedicinefordiagnosticpurposes.
1.Labelledcyanocobalaminefindsuseformeasuringtheglomerularfiltrationrate.
2.Ferriccitrateinjectionfindsuseforthediagnosisofhaematologicaldisorders.
3.Colloidalgoldinjectionisuseddiagnosticallytostudybloodcirculationinliver.
4.Sodiumiodideinjectionfindsuseindiagnosisofproperfunctioningofthyroid
gland.
5.Sodiumiodohippurateinjectionfindsuseinthestudyofrenalfunction.
6.SodiumroseBengalinjectionfindsuseasdiagnosticagenttotestliverfunction.
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24. III) In research:
Excellentbiologicalandmedicinalstudieshavebeencarriedoutwithradioactive
isotopesastracers.
IV)Sterilization:
Excellentuseisbeingmadeoftheradiationconstantlyavailablefromsomestrong
radiationsourceforsterilizingpharmaceuticalsintheirfinalpackedcontainersand
surgicalinstrumentsinhospitals.
Noheatorchemicalgetsinvolved.
Thermolabilesubstanceslikevitamins,hormonesantibioticscanbesafelysterilized.
Findsuseinsterilizationofpharmaceuticals.
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Calcium (Ca-44 and Ca-45)Theradioactivecalciumhasbeenusedtostudybone
structureandintreatmentofcarcinomaofbone.
Strontium -90 Usedintheradiotherapyofsuperficialcarcinomas.
Cyanocobalamine(Co-57)Usedinthediagnosisofperniciousanaemia.
Calcium -47 Itishavinghalflifeof4.7days.Itisusedincalcium
absorptionstudies.
Cyanocobalamine
(Co-60Solution USP)
UsedtostudyabsorptionanddepositionofvitaminB12
innormalindividuals.
Gold (Au-198)solution Findsuseinestimationofreticuloendothelialactivity.
Iron (Fe-59) Findsuseinresearchstudiesaboututilizationand
absorptionofIronsalts.

26. Measurement of Radioactivity
Tomeasuretheradiationsofalpha,betaandgammaparticles,many
techniquesinvolvingdetectionandcountingofindividualparticlesor
photonsareused.
Themethodselectedforthemeasurementofradioactivitydependsupon
theextentofenergydissipationandpenetrabilityofradiation.
Gas ionization devices:
1)Ionization chambers
2)Proportional counters
3)Geiger Muller counters
4)Scintillation Counters
5)Autoradiography
6)Solid state detectors
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1)Ionisation Chambers:
Theyareavailableinvariousshapesandsizes.
Anionizationchamberconsistsofachambersfilledwithgasandfittedwithtwo
electrodeskeptatdifferentelectricalpotentialsandameasuringdeviceto
indicatetheflowofelectriccurrent
Radiationbringsaboutionizationofgasmoleculesorionswhichcauseemission
ofelectronswhichinturnrevealsthechangesinelectricalpotential.

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2) Proportional counters:
Theyaremodifiedionizationchambersinwhichanappliedpotentialionizationof
primaryelectronscausesproductionofmorefreeelectronswhichgetscarriedto
theanode.
Foreachprimaryelectronliberated,muchmoreadditionalelectronsget
liberated,thecurrentpulsethroughelectricalcircuitisgreatlyamplified.
Thevoltagerangeoverwhichthegasamplification(ionization)occursiscalled
theproportionalregion,andthecountersworkinginthisregionarecalled
Proportionalcounters.

29. 3) Geiger-Muller Counter
Thesearemostpopularradiationdetectors.
Theydonotneedtheuseofhighgainamplifier.
Theycandetectalpha,betaandgammaradiations.
Geiger-Mullercounterishavingionizinggasandisalsohavingaquenching
vapourwhosefunctionsare:
1.Topreventthespuriouspulsesthatmaygetproducedduetothepositiveions
(cations)reachingthecathode(-electrode).
2.Toabsorbthephotonsemittedbyexcitedatomsandmoleculesreturningtotheir
groundstate.
Chlorineandbrominearegenerallyusedasquenchingagent.
Ethylalcoholandethylformateareusedasorganicquenchingagents.
Thefillinggaspressurehasbeenmuchbelowtheatmosphericpressuretoavoiduse
ofhighoperatingvoltages.
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30. Construction:
AGMCounterpossessesacylindricalcathode(-electrode),whichisusually
1-2cmindiameter,alongthecentreofwhichisawireanode(+electrode).
Thespaceisfilledwithaspecialgasmixturewhichgetsreadilyionized
together,withasmallproportionofquenchingvapour.
Forsolidradioactivesources:
Forsolidradioactivesources,theendwindowtypeGMcounterhasbeenthemost
popular.
Thewindowhasbeenmadeofanaluminiumalloy,micaorathinglassbubble.
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31. In order to count the medium and high energy beta particles and for gamma counting, thin
glass walled counters may be used.
They are normally 1 cm in diameter and having a glass wall of 20 –40 mg cm
-2
thickness.
The tube is coated on the inside to form the cathode.
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32. For radioactive liquid sources:
Itishavingacapacityof10cm
3
inannularspace.Insuchacounter10cm
3
of3%
solutionofUraniumsaltgivesnearly10,000countsperminute.
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33. Operation:
Whenionizingradiationsuchasalpha,betaorgammaparticleentersthetube,itcanionize
someofthegasmoleculesinthetube.
Fromtheseionizedatoms,anelectronisknockedoutoftheatomandsotheremaining
atomispositivelycharged.
Thehighvoltageinthetubeproducesanelectricfieldinsidethetube.
Theelectronsthatwereknockedoutoftheatomareattractedtothepositiveelectrode
(anode)andthepositivelychargedionsareattractedtothenegativeelectrode(cathode)
Thisproducesapulseofcurrentinthewiresconnectingtheelectrodesanthispulseis
counted.
Afterthepulseiscounted,thechargedionsbecomeneutralizedandtheGeigercounteris
readytorecordanotherpulse.
InorderfortheGeigertubetorestoreitselfquicklytoitsoriginalstateafterradiationhas
entered,agasisaddedtothetube.
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34. ForproperuseoftheGeigercounter,onemusthaveappropriatevoltageacrossthe
electrodes.
Ifthevoltageistoolow,theelectricfieldinthetubeistooweaktocauseacurrentpulse.
Ifthevoltageistoohigh,thetubewillundergocontinuousdischargeanditwillbe
damaged.
Forlowvoltages,nocountsarerecorded.Thisisbecausetheelectricfieldistooweakfor
evenonepulsetoberecorded.Asthevoltageisincreased,oneobtainsacountingrate.
ThevoltageatwhichtheGMtubejustbeginstocountiscalledthestatingpotential.The
countingratequicklyrisesasthevoltageisincreased.
Theriseissofastthatthegraphlookslikeasteppotential.
Afterthequickrise,thecountingratelevels0.Thisrangeofvoltagesistermedaspleateau
region.
Eventuallythevoltagebecomestoohighandwehavecontinuousdischarge.
Thethresholdvoltageisthevoltagewheretheplateauregionbegins.Properoperationis
whenthevoltageisintheplateauregionofthecurve.
Forbestoperation,voltageshouldbeselectedfairlyclosetothethresholdvoltage.
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Scintillation counters: (For gamma counting)
Whenradiationisincidentoncertainsubstancessuchasphosphor,aflashoflightis
givenout.Itthusbecomespossibletomeasurealpha,betaandgammaradiationsby
scintillationdetectorsprovidedthedetectorhasbeensuitablymodifiedforthetypeof
radiationtobemeasured.
Thescintillationcounterconsistsofacell,aphotomultipliertubewhichiscoupled
withphosphororfluorescentmaterialtoconvertscintillationintoelectricalpulses,
amplifierandscaler

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Radio-opaque contrast media
Radio-opaque substances are those compounds (both inorganic and organic) which
are having the property of casting a shadow on X-ray films.
These compounds have the ability to stop the passage of X-rays and appear opaque
on X-ray examination.
BARIUM SULPHATE
Formula: BaSO
4
Preparation:
1.For pharmaceutical purposes, Barium sulphate is prepared by treating an aqueous
solution containing Barium ions with a solution containing sulphate ions.
Ba(OH)
2+ H
2SO
4----------------BaSO
4+ 2H
2O
BaCl
2+ H
2SO
4----------------BaSO
4+ 2HCl
The precipitated salt is washed, dried and screened.
2. It is also prepared by the action of dilute H
2SO
4on BaS
BaS+ H
2SO
4 -----------------BaSO
4+ H
2S

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Properties:
Heavy
Fine white bulky powder
Odourless
Tasteless
Free from grittiness
Insoluble in water
It may be solubilized by fusing with alkali carbonates.
Uses:
It is used as a diagnostic drug which is used medicinally in X ray examination.
It is administered by enema before X ray examination in the form of Barium meal to
make intestinal tract opaque to X rays, so that it can be photographed.

39. Thank You
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