This document discusses the use of nanomaterials in radiochemical separations for biomedical applications. It summarizes the development of four radiochemical separation systems/generators using nanomaterials: 1) 99Mo/99mTc generator for SPECT imaging, 2) 68Ge/68Ga generator for PET imaging, 3) 188W/188Re generator for therapy, and 4) 77Ge/77As generator. The nanomaterial-based generators demonstrated excellent separation yields and purity of daughter radionuclides, as well as consistent performance throughout shelf-life. This novel approach overcomes limitations of conventional generators and establishes protocols for global acceptance of new radiochemical separation systems.

1. Role of Nanomaterials in RadiochemicalRole of Nanomaterials in Radiochemical
Separations for Biomedical Applications:Separations for Biomedical Applications:
Present status and future perspectivesPresent status and future perspectives
Rubel ChakravartyRubel Chakravarty
Radiopharmaceuticals DivisionRadiopharmaceuticals Division
Bhabha Atomic Research Centre, Mumbai, IndiaBhabha Atomic Research Centre, Mumbai, India
EE--Mail: rubelc@barc.gov.inMail: rubelc@barc.gov.in
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2. Radiochemical Separations: The considerationsRadiochemical Separations: The considerations
Chemical
Separation
Radiochemical
separation
Large no. of atoms Small no. of atoms
Wide range of
process can be
adopted
Simple process with
minimum variables
and manipulations
No dose Radiation dose
No time constraint ALARA
Type and composition of the solution or matrix
Type of radiation emitted by the radionuclide and its decay products
Half life of the radionuclide
Specific activity of the radionuclide
Radioactivity level
Feasibility of separation with high radionuclidic, radiochemical and chemical purity
Amenability for preparation of radiopharmaceuticals
Sterility and apyrogenicity of the final product
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3. Radionuclide generators: The most importantRadionuclide generators: The most important
radiochemical separation systems used in Nuclearradiochemical separation systems used in Nuclear
MedicineMedicine
Parent and daughter
radionuclides in a
state of radioactive
equilibrium
Separation of daughterSeparation of daughter
from parent: Difference
in chemical properties
Milking ‘cow’ analogy
Repeated growth and re-
elution
The original 99Mo/99mTc generator:
Brookhaven National Lab., 1960
Radioactive equilibrium and repeated elutions
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4. Radionuclide generators: The availableRadionuclide generators: The available
optionsoptions
Type of generator Advantages Disadvantages
Chromatographic Simple, easy to operate Sorption capacity
restriction, chemical
impurities, radiolytic
damage to column
matrix, post-elution
concentration and
purification of eluatepurification of eluate
Solvent Extraction Low specific activity
parent can be used
Cumbersome multi-step
process, added chemical
impurities, radiation
exposure
Sublimation Low specific activity
parent can be used
Cumbersome,
dangerous, limited
scope, low shelf-life
Gel type Simple, easy to operate,
medium specific activity
parent can be used
Parent breakthrough,
limited scope, limited
shelf-life
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5. Nanomaterials based chromatographicNanomaterials based chromatographic
approachapproach
Principle:
Based on high surface
area
Enhanced selectivity
Increased active surface
sites
Increased active surface
sites
Advantages:
High sorption capacity
Excellent selectivity for
parent
High radioactive
concentration and purity
of eluate
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6. Synthesis and structural characteristicsSynthesis and structural characteristics
ofof nanosorbentsnanosorbents
Nanosorbent Synthesis
method
Structure Average
crystallite
size (nm)
Surface area
(m2 g-1)
TiP Controlled
hydrolysis of TiCl4
in isopropyl
alcohol
Rutile TiO2 5±2 38±5
t-ZrO2 Controlled Tetragonal 7±3 340±15
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t-ZrO2 Controlled
hydrolysis of
ZrOCl2
Tetragonal
ZrO2
7±3 340±15
CeO2-PAN Decomposition of
cerium oxalate
precursor;
incorporation in
PAN matrix
Cubic CeO2 10±1 72±5
γγγγ-Al2O3 Mechanochemical γγγγ-Al2O3 3±1 272±7

7. 9999Mo/Mo/99m99mTc generatorTc generator
99mTc: The ‘work horse’ of Nuclear
Medicine
Alumina based column generator
Limited sorption capacity of alumina
(2-20 mg Mo/g)
Requires high specific activity 99MoRequires high specific activity 99Mo
produced through fission route
Technology for production of fission
99Mo is unable to most of the countries
Use of low specific activity (n,γγγγ) 99Mo:
A prudent approach
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8. NanosorbentsNanosorbents basedbased 9999Mo/Mo/99m99mTc generatorTc generator
Specific activity of 99Mo = 400 mCi/g
Amount of sorbent = 5 g
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Activityofgenerator(mCi)

9. 188188W/W/188188Re generatorRe generator
188Re: An important therapeutic isotope
The most common option: Alumina based
generator
Limited sorption capacity of alumina: ~50
mg W/g
Requires very high specific activity 188W:
High Flux Reactors (~1015 ncm-2s-1)
Only three high flux reactors in world
Uneconomical due to limited availability
of 188W
Use of medium specific activity 188W
producible in ~50 research reactors in the
world
HFIR, USA SM Reactor, Russia
BR2 Reactor, Belgium
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10. NanosorbentsNanosorbents basedbased 188188W/W/188188Re generatorRe generator
Sorbent
material
Synthesis
method
Sorption capacity
(mg W/g)
Reference
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material method (mg W/g)
Static Dynamic
PZC Polymerization
of Zr
483 # J. Nucl. Radiochem.
Sci., 6, 189 (2005)
PTC Polymerization
of Ti
515 # Sep. Sci. Technol.,
44, 1074 (2009)
Synthetic
alumina
Sulfation of
alumina
465 180* U.S. Patent
2010/02489855A1
TiP Hydrolysis of
TiCl4 in
isopropyl
alcohol
325 102 J. Nanosci.
Nanotechnol., 8,
4447 (2008)
Nano-ZrO2 Hydrolysis of
ZrOCl2
300 120 Appl. Radiat. Isot.,
68, 229 (2010)
γγγγ-Al2O3 Controlled
hydrolysis of
Al(NO3)3
512 300 Anal Chem . 83,
6342 (2011)
*Data calculated from the information provided (U.S. Patent
2010/02489855A1); #Not reported

11. 6868Ge/Ge/6868Ga generatorGa generator
68Ga: An important PET radioisotope
The most common options: TiO2 or SnO2
based generator
68Ga obtained is not directly suitable for
preparation of radiopharmaceuticals
Chemical impurities due to degradation
and dissolution of column matrix
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and dissolution of column matrix
Post elution processing of 68Ga:
Cumbersome and added chemical
impurities
Limited shelf-life of the generator:
Degrading performance after successive
elutions
Use of selective and chemically stable
nanomaterial based sorbents

12. NanosorbentsNanosorbents basedbased 6868Ge/Ge/6868Ga generatorGa generator
First reported systems where 68Ga availed from the
68Ge/68Ga generator could be directly used for
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Ge/ Ga generator could be directly used for
radiopharmaceutical applications !!!
0 50 100 150 200 250 300 350 400
0
20
40
60
80
100
Yieldof
68
Ga(%)
Time of elution (days)
0
2
4
6
8
10
Elution performance of the generator over 1 y
68
Gein
68
Ga(10
-5
%)

13. Separation ofSeparation of 7777As from (n,As from (n,γγ)) GeGe
Funnel for
introducing
reagent
Funnel for
introducing
77As: A medium energy β- emitter
76Ge 77mGe
77As77Ge76Ge 77Se
+ n
+ n
σ ~ 90 mb
σ ~ 60 mb
t1/2 = 53 s
t1/2 = 38 ht1/2 = 11.8 h
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Vaccum
or
compressed
air
reagent
Funnel for
introducing
reagent
Glass frit
As in
0.1 M NaOH
77
As solution
at pH=10
77
0.1 M NaOH
Vaccum
or
compressed
air
Target (GeO )
dissolution flask
2
TiP
TiP
Glass frit
Vaccum
or
compressed
air
introducing
reagent
Overall radiochemical yield of 77As was >80%

14. Summary and future perspectivesSummary and future perspectives
A novel concept in the field of radionuclide generators and radiochemical separations
Four medically useful radiochemical separation systems/ generators were developed
Diagnostic: 99Mo/99mTc (SPECT) and 68Ge/68Ga (PET)
Therapeutic: 188W/188Re and 77Ge/77As
Excellent separation yield and purity of daughter radioisotopes
Consistent performance throughout the shelf-lives of the respective generators
Overcomes the limitations of the present day generators to a great extent
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Established protocol
No additional manpower required
No change in operating strategies from the conventional bulk sorbent based systems
Existing automated generator systems can be used
Global acceptance
Other potential radiochemical systems where this strategy can be explored:
90Sr/90Y generator, 103Ru/103mRh generator, separation of NCA 177Lu from 177Yb, pre-
concentration and purifications of radiochemicals prior to preparation of
radiopharmaceuticals

15. AcknowledgementsAcknowledgements
Radiopharmaceuticals
Division, BARC
Chemistry Division,
BARC
Society of Materials Chemistry, India
Prof. M.R.A. Pillai, Head, Radiopharmaceuticals Division, BARC
Prof. Ashutosh Dash, Radiopharmaceuticals Division, BARC
Prof. A.K. Tyagi, Chemistry Division, BARC
Shri Rakesh Shukla, Chemistry Division, BARC
All co-authors in the publications
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Division, BARC

16. THANK YOU FOR YOUR ATTENTIONTHANK YOU FOR YOUR ATTENTION!
rubelc@barc.gov.in
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