Subido por Victoria Cruz Romano

Adsorbentes basados en nanomateriales

J Radioanal Nucl Chem (2014) 299:741–757
DOI 10.1007/s10967-013-2823-1
Nanomaterial-based adsorbents: the prospect of developing new
generation radionuclide generators to meet future research
and clinical demands
Rubel Chakravarty • Ashutosh Dash
Received: 5 August 2013 / Published online: 14 November 2013
Akadémiai Kiadó, Budapest, Hungary 2013
Abstract Nanostructured materials by virtue of huge
surface to volume ratios, altered physical properties, tailored surface chemistry, favorable adsorption characteristics, and enhanced surface reactivity resulting from the
nanoscale dimensions, have attracted considerable attention
as a new class of adsorbent material in column chromatographic separation. This emerging class of adsorbent represents an innovative paradigm and is expected to play an
important role in the development of radionuclide generators for nuclear medicine. The optimal combination of
suitable nanomaterial and appropriate parent/daughter
radionuclide pair forms the basis of such generators.
Development of such generators is currently under intensive
investigations and the utility of such systems is expected to
pave the way for broad panoply of diagnostic and therapeutic applications in nuclear medicine. While nanomaterial-based radionuclide generator is still in its infancy, the
use of such novel class of adsorbents is expected to have
potential impact on shaping the radionuclide generator
technology of future generation. This review provides a
comprehensive summary on the utility of nanomaterials as
effective adsorbents in the development column chromatographic radionuclide generators for medical applications. This overview outlines a critical assessment of role of
the nanosorbents, recent developments, the contemporary
status, and key challenges and apertures to the near future.
Keywords Adsorbent Column chromatographic
separation Nanomaterials Radionuclidic generator Radiopharmaceuticals
R. Chakravarty A. Dash (&)
Isotope Applications and Radiopharmaceuticals Division,
Bhabha Atomic Research Centre, Mumbai 400 085, India
e-mail: [email protected]
The role of radionuclide generator in nuclear medicine in
providing radionuclides for both research and clinical
applications has been well demonstrated and recognized
[1–4]. Generator produced radionuclides find extensive
utility in nuclear medicine, oncology and interventional
specialties. Widespread interest in the use of radionuclide
generators to obtain a variety of diagnostic and therapeutic
radionuclides to meet the needs of nuclear medicine have
stimulated considerable research leading to the development of several innovative strategies [4–6]. The current
importance and success of diagnostic radionuclide imaging
using nuclear medicine techniques is primarily due to the
availability of 99Mo/99mTc generator system [7–10].
The selection of an appropriate separation technology to
isolate the daughter radionuclide of required purity with
appreciable yield has been the cornerstone in the success of
a radionuclide generator [11]. While numerous separation
technologies have been investigated and effectively used
over the years for achieving the separation of radionuclide
of interest, the column chromatography technology has
dominated the field significantly due to the following
Simple and user friendly process, requiring minimum
time for operation.
Reproducible performance in terms of daughter radionuclide elution yields on continual use.
High radionuclidic (RN), radiochemical (RC) and
chemical purity of the daughter radionuclide are
Generate insignificant quantity of radioactive waste.
Negligible operational constraints.
Offer the possibility of regeneration and recharging.
For these reasons, radionuclide generators making use of
column chromatography technique have been in use for
several years and have offered substantial benefits for
nuclear medicine applications by providing short-lived radionuclides for the onsite formulation of radiopharmaceuticals for a variety of diagnostic and therapeutic
applications [2, 12]. The tremendous prospects along with
the challenges associated with the development of radionuclide generator of desired attributes have thus led to a
considerable amount of fascinating research and innovative
strategies. Among the various separation technologies
available, the operational simplicity of the well established
chromatographic-type generator using a solid parent
adsorption material is the preferred method of choice for
radionuclide generator from which the daughter radionuclide formed from the decay of its generic parent radionuclide is selectively eluted. Within the heart of column
chromatography separation technique lays the adsorbent
and the ability of the adsorbent to separate the daughter
radionuclide constitutes the pillars for its success in
radionuclide generator. With substantial efforts by both
academia and the industry, a wide variety of adsorbents
with appropriate physicochemical properties have been
successfully developed and used in a wide range of
radionuclide generators [4, 12, 13]. The required volume
for quantitative elution of daughter radionuclide from a
chromatographic-based generator apparently depends on
the size of the column which, in turn, is inversely proportional to the specific activity of the parent. In view of
the limited adsorption capacity of adsorbents derived from
bulk material, the use of high specific activity parent
radionuclide is not only an interesting prospect, but may be
viewed as a necessary one owing to the requirement to
obtain high radioactive concentration (RAC) or specific
volume of the daughter radionuclide to prepare radiopharmaceuticals. Despite the potential advantages of column chromatography separation technique, the use of low
specific activity parent radionuclide poses numerous challenges and hurdles. In light of the perceived need to adsorb
required amount of activity in a generator, the use of low
specific activity parent radionuclide necessitates large
amount of adsorbent which in turn increases the size of the
column. Elution of the daughter radionuclide from such
generator requires a large volume of eluent and results in a
solution of low specific volume activity (low RAC) which
is unsuitable for subsequent chemical attachment of
daughter radionuclide to an agent for clinical use. While
post elution concentration (PEC) of generator eluate [13–22]
has tangible benefits to render them useful for radiopharmaceuticals applications, use of high capacity adsorbent in
a small size chromatography column is a trustworthy
proposition. The development of high capacity adsorbent
represents an important challenge and can only be
J Radioanal Nucl Chem (2014) 299:741–757
overcome by technical breakthroughs in areas of material
The past few decades have witnessed unprecedented
endeavors for developing a wide variety of high capacity
adsorbent materials in attempts to improve the specific
volume activity of the generator eluate [12, 23]. Yet, in
spite of many impressive advances in the development and
use of high capacity adsorbent, the promise to develop a
practical high capacity adsorbent suitable for radionuclide
generator application has not been fulfilled. While the
attempt made in this direction constitutes a step in the right
direction, all the efforts turned out futile as the adsorption
capacity of bulk material cannot be improved beyond
certain degree owing to the limitation posed by the density
of surface active sites, the activation energy of adsorptive
bonds and the mass transfer rate to the adsorbent surface.
A more prudent approach to mitigate these unforeseen
difficulties is to identify the prospect of using nanomaterial
as a new generation adsorbent. Nanomaterials differ from
microsized and bulk materials not only in the scale of their
characteristic dimensions, but also in the fact that they
possess new physical properties and offer new possibilities
for developing high capacity adsorbent. The enhancement
in specific surface area and associated improved surface
energy offers a great deal of advantages and renders some
very important properties. The use of nanoparticles as
effective adsorbents requires careful synthesis, structural
characterization, detailed adsorption properties analysis,
and reproducible scale-up and manufacturing process to
achieve a consistent product with the intended physicochemical characteristics.
The recent surge of interest in the use of nanomaterialbased adsorbent in the preparation of column chromatography radionuclide generators has been the motivation to
provide this detailed review on this emerging field of
technology. It is not a comprehensive review but rather
discusses key developments and applications. In the following sections, the radionuclide generator principle, role
of nanomaterial-based adsorbent in the development of
radionuclide generators, different types of nanomaterialbased radionuclide generators, current status, survey of
major strategies for enhancing their utilities, and future
prospective are discussed.
Principle of a radionuclide generator system
A radionuclide generator (Fig. 1) is a self-contained system
housing an equilibrium mixture of a parent/daughter
radionuclide pair. The system is designed to separate and
provide the daughter radionuclide formed by the decay of a
parent radionuclide [1, 4, 11, 23, 24]. The parent–daughter
nuclear relationships offer the possibility to provide
J Radioanal Nucl Chem (2014) 299:741–757
Radioactive equilibrium
The daughter radionuclide formed from the decay of a
parent radionuclide. The decay of parent radionuclide can
be mathematically expressed by the Eq. (1):
¼ k1 N1 ;
N1 ¼ N10 ek1 t ;
where k1 is the decay constant for the parent radionuclide
and N1 represents the number of atoms of parent at time t.
The N10 term indicates the corresponding quantity when
t = 0.
The daughter radionuclide formed from the decay of the
parent, k1N1, also decays at a rate, k2N2 and thus the net
production rate of the daughter radionuclide is given by
Eq. (2):
¼ k1 N1 k2 N2 ¼ k1 N10 ek1 t k2 N20 ek2 t :
Solution of this linear differential equation leads to:
N2 ¼
N10 ek1 t ek2 t þ N20 ek2 t :
k2 k1
For radionuclide generator application, the half life of
the parent radionuclide should be greater than that of the
daughter (t1/2,1 [ t1/2,2, i.e. k1 \ k2) to allow repeat elution
of the daughter radionuclide over a reasonable shelf-life
period. Thus, ek2 t is negligible compared with ek1 t after t
becomes sufficiently large and the N20 ek2 t term also
becomes negligible and therefore the Eq. (2) can be
simplified as below:
Fig. 1 Schematic diagram of a chromatography radionuclide generator, a generator assembly and b generator column
radionuclide generators to separate the short-lived daughter
at suitable time intervals.
Advantages of radionuclide generators are as follows:
Ensures onsite availability of short lived daughter
radionuclides on demand for diagnostic and therapeutic
applications without reliance on local accelerator or
reactor production capabilities.
Ease of availing short lived daughter radionuclides in a
cost-effective way for the onsite formulation of
Availability of the daughter radionuclide in a high
specific activity, no-carrier-added (NCA) form.
Provide the scope of performing diagnosis and therapy
in places far from isotope production facilities.
However, the radionuclide generators intended for
medical applications must meet regulatory and quality
control requirements.
N2 ¼
N 0 ek1 t :
k2 k1 1
Since, N1 ¼ N10 ek1 t ; the ratio of the number of atoms of
the two radionuclides can be expressed as:
N1 k2 k1
N1 k1 k2 k1 A1 ðk2 k1 Þ
¼1 :
N2 k2
A1 and A2 refer to the activities of the parent and
daughter radionuclide, respectively.
The daughter activity reaches the state of equilibrium or
maximum activity, when its formation is exactly compensating those which are decaying:
When A1 ¼ A2
or k1 N1 ¼ k2 N2
¼ 0:
This condition of a constant ratio for the parent and
daughter activity is known as radioactive equilibrium, and
the maximum activity of the daughter which occurs at the
time of equilibrium t is given by:
J Radioanal Nucl Chem (2014) 299:741–757
activity is at its maximum as calculated using Eq. (7).
Owing to the decrease of the parent radionuclide activity
within the time between two elution steps, the radionuclide
generator is expected to provide a reduced level of the
daughter radionuclide activity by each subsequent elution
as shown in Fig. 3.
In-growth and isolation of daughter radionuclide
Fig. 2 Schematic diagram of secular and transient equilibrium.
a Transient equilibrium is a condition when the t1/2(phys) of the
parent is approximately 10 times greater than the t1/2(phys) of the
daughter. b Secular equilibrium is a condition when the t1/2(phys) of the
parent is many times greater than the t1/2(phys) of the daughter
(100–1,000 times greater or more)
ln :
k2 k1 k1
Radioactive equilibrium between the parent and
daughter is referred to as transient or secular equilibrium,
depending on the relative half lives of the parent and
daughter pair. In transient equilibrium, the ratio between
the half lives of the parent and daughter is less than 10. For
a secular equilibrium, the parent half life is far higher than
the daughter half life (t1/2,1 t1/2,2 or k1 k2), the Eqs.
(5) and (6) reduce to N1/N2 = k2/k1 and A1 = A2. Hence,
in secular equilibrium, the daughter activity is equal to the
parent activity.
Illustration of the relative growth and decay of the
parent and daughter radionuclide pair is illustrated in
Fig. 2a (transient equilibrium) and Fig. 2b for secular
equilibrium. The daughter radionuclide can be repeatedly
extracted from parent/daughter radionuclide pair, which is
the main benefit of using these systems for medical and
industrial applications.
For practical considerations, radionuclide generators are
eluted at periodic intervals depending on the daughter
activity requirements. Often the separation of the daughter
from the parent may not occur at the time the daughter
The growth and separation of the daughter radionuclide can
be continued as long as there are useful activity levels of
the parent radionuclide available. Elution of the generator
is performed either manually or with an automated system.
The activity eluted from the generator typically follows a
Gaussian distribution with the maximum activity being
eluted in the intermediate fractions. The eluent can also be
‘fractionated’ by discarding those fractions with low
activity if the activity concentration is a critical issue.
Separation may be performed any time before equilibrium
is reached, and the activity levels of daughter recovered
will depend on the time elapsed since the last separation.
In-growth of the daughter species is continuous, and once
the activity of the daughter is recovered from the mixture,
the daughter activity increases until its activity level
reaches a maximum and is in equilibrium with the parent
radionuclide (Fig. 2). The growth of the daughter depends
on the half life of the daughter radionuclide which also
governs the frequency of its separation from the parent
radionuclide. When the daughter radionuclide is relatively
long-lived, periodic elution will take place prior to reaching the maximum equilibrium daughter activity levels and
it is normal to use generators in this way. As an example,
50 % daughter activity in-growth is detected in one half
life, 75 % in two half lives and the daughter activity
reaches the activity of the parent radionuclide in five–six
half lives (Fig. 4).
Criteria for selection of parent/daughter pairs
Although an examination of the chart of the radionuclide
indicates that there are about 130 parent/daughter pairs of
radionuclides that can be used for the preparation of
radionuclide generators, only a few are of practical interest.
While selecting a parent/daughter pair for making radionuclide generator, the following criteria need to be
Availability of parent radionuclide: Cost-effective production of the parent radionuclides is important. Parent
radionuclide which exhibits attractive characteristics but
which lack a cost effective production route will
constitute a major barrier for its utility in radionuclide
J Radioanal Nucl Chem (2014) 299:741–757
Fig. 3 Multiple growth and
elution of daughter activity in a
radionuclide generator
Fig. 4 The growth of daughter radionuclide in a radionuclide
generator as a function of time (t1/2)
Parent radionuclide half life: The physical half-life of
the parent radionuclide should be long enough to
provide long practical shelf-lives of the generator.
Parent specific activity: The specific activity of the
parent radionuclide should be high to retain required
activity in a given mass of adsorbent.
Daughter radionuclide half life: The physical half-life
of the daughter radionuclide should be matched well
with the in vivo pharmacokinetics of the radiolabeled
targeting molecule.
Emission and energy of the radiation of the daughter
radionuclide: The daughter product of a radionuclide
generator will decay by any of the decay modes
(isomeric transition, b-, b?, electron capture, a decay)
or by a combination of decay modes. Consequently, the
applications of generators vary depending on the decay
characteristics. c Emitters, with c energy within the
range of 100–250 keV are suitable for SPECT imaging.
Particle emitting radionuclides (a particle, b- particle
or Auger electron emitters) are suitable for therapy.
Positron emitting radionuclides are needed for positron
emission tomography (PET) imaging.
Decay of daughter radionuclide: The daughter radionuclide should preferably decay to a stable or very
long-lived product to preclude radiation dose to the
patient undergoing diagnosis or therapy.
Purity of daughter radionuclide: The daughter radionuclide eluted from the generator should be of high
purity (RN, RC, and elemental purity) and free from
trace metal contamination.
Chemical characteristics of daughter radionuclide: The
daughter radionuclide should have chemistry amenable
to its attachment with a broad class of carrier molecules
and binding must exhibit high in vivo stability when
attached to the radiopharmaceutical.
Table 1 summarizes the characteristics of several key
radionuclide generator systems that could be useful to
provide daughter radionuclide for life science applications.
While devising a radionuclide generator system, the
following points should be taken into consideration.
Chemical or physical properties of the daughter radionuclide must be sufficiently different from that of the
parent to permit easy and efficient separation using
appropriate chemical or physical techniques.
Separation must be performed rapidly to minimize
decay losses of the daughter radionuclide.
The daughter radionuclide should be separated with
0.9 % NaCl or in a chemical form amenable for the
radiolabeling with a broad class of carrier molecules.
Yield and purity of the daughter radionuclide intended
for radiotracer investigation should be within the
acceptable range.
Physical intervention with the generator/elution system
should be minimal to minimize radiation dose to
operating staff.
J Radioanal Nucl Chem (2014) 299:741–757
Table 1 Radionuclide generators for biomedical applications
Generator systems
Parent radionuclide
Daughter radionuclide
Principal production
Main decay
Main decay
32.9 years
12.36 h
47.3 years
3.93 h
8.28 h
270.8 days
21.1 min
1.14 h
8.4 days
1.08 days
Ti/ Sc
86.2 days
1.86 h
25.6 days
1.27 min
28.5 years
2.67 days
2.75 days
6.01 h
16.97 days
R, A
56.12 min
c, Ae
1.267 years
39.6 s
115.1 days
1.66 h
6.00 days
3.6 min
3.26 days
2.28 h
c, b-
30.0 years
2.55 min
In vivo diagnosis
12.75 days
1.68 days
c, b-
3.16 days
6.4 min
284.9 days
3.37 days
17.3 min
3.39 min
b?, Ae
3.40 days
1.12 days
9.24 days
2.28 s
1.87 years
6.70 days
21.5 days
9.31 min
69.4 days
16.98 h
15.4 days
4.94 s
6.0 years
19.15 h
c, b-
1.6 9 103 years
3.83 days
10.0 days
45.6 min
b-, a
A accelerator, DC decay chain, f fission, R reactor/neutron capture, FP fission product, Ae atomic electrons, EC electron capture, b1 if
EC \50 %, ERT endoradiotherapy, FPRNA first pass radionuclide angiography, PET positron emission tomography, RPC radiopharmaceutical
chemistry, SPECT single photon emission computed tomography
Processes for the production of radionuclide generator
systems for clinical applications should follow good
manufacturing practice standards.
Nanomaterial-based adsorbent
Nanomaterials are materials with a particle size of less than
100 nm in at least one dimension and have drawn the
attention, imagination, and close scrutiny of scientists of
diverse fields [24–32]. When the characteristic dimensions
changes to nanoscale, they make up a new realm of matter
that results in:
large fraction of surface atoms,
high surface energy,
spatial confinement,
reduced imperfections.
As a result, these materials possess unique physical
properties and offer possibilities to develop new technologies and improve the existing ones. The high surface area
to-mass ratio of nanomaterials can greatly improve the
adsorption capacities of sorbent materials. Because of their
reduced size and large radii of curvature, the nanomaterials
have a reactive surface due to the high density of lowcoordinated atoms at the surface, edges and vortices. The
surface atoms are unsaturated and can therefore bind with
other atoms, possess highly chemical activity and can
strongly chemisorb many substances.
J Radioanal Nucl Chem (2014) 299:741–757
Table 2 Synthesis and structural characterization of nanosorbents for radionuclide generators
Synthesis method
Structural characteristics
generators reported
using this material
Polymer embedded
titania (TiP)
Controlled hydrolysis of TiCl4 in
isopropyl alcohol medium
Nanocrystalline, rutile phase, 5 nm
crystallite size, surface area 30 m2/g
[43, 44]
Mixed phase
zirconia (nanoZrO2)
Controlled hydrolysis of ZrOCl28H2O
in isopropyl alcohol medium
Nanocrystalline, biphasic with monoclinic
phase as major, 15 nm crystallite size,
surface area 45 m2/g
zirconia (t-ZrO2)
Controlled hydrolysis of ZrOCl28H2O
in ammonical medium
Nanocrystalline, tetragonal phase, 7 nm
crystallite size, surface area 340 m2/g
[39, 41]
alumina (c-Al2O3)
Mechanochemical reaction of
aluminum nitrate with ammonium
Nanocrystalline, c-phase, 2 nm crystallite
size, surface area 250 m2/g
composite (CeO2–
Decomposition of cerium oxalate
precursor followed by incorporation
in polyacrylonitrile matrix
Nanocrystalline, 10 nm crystallite size,
surface area 72 m2/g
The advantages for using nanomaterials as adsorbent in
column chromatographic radionuclide generator are due to
Exceptional adsorption capabilities.
Large surface area to attain high adsorption capacity.
Fast adsorption kinetics due to absence of internal diffusion
resistance to achieve rapid equilibrium conditions.
Selectivity towards certain radionuclides.
Favorable radiation, mechanical and thermal stabilities.
Possibility for regeneration and reusability.
The performance of adsorbent media in a fixed bed
column depends mainly on two factors: the adsorption
capacity of the media and its mass transport kinetics. Since
both the factors can be limiting, fixed bed adsorption media
can be designed using nanomaterials. This in turn would
maximize the mass transport kinetics by providing radionuclides with rapid access to the sorption sites due to high
surface area of the nanomaterial and by promoting internal
mass transport due to its porosity.
For successful use of nanomaterial-based adsorbents in
radionuclide generator applications, a number of factors
should be carefully considered with the most important
amongst them being:
Chemical composition,
Surface area and porosity of the material,
Granular properties,
Chemical durability,
Adsorption characteristics in aqueous medium.
While the adsorption of ionic species of radionuclides
from solution on the nanoadsorbent is essentially
[36, 38]
[35, 40]
controlled by electrostatic forces, the primary interactions
between radionuclide and sorbent are mainly due to the
following parameters.
Physical adsorption or chemisorption of ion (dipole–
dipole interaction).
Ion-exchange process with the participation of surface
groups or oxygen-containing surface groups.
Formation of surface complexes and hydroxo
In radionuclide generator applications, the parent
radionuclide from solution is preferentially retained by the
chromatographic column containing nanomaterial by
adsorption. Nanomaterials provide almost unlimited combinations of various compositions, sizes and dimensions of
materials, which can be tailored to develop a wide range of
radionuclide generators with desired properties [24, 33].
Potentially useful radionuclide generator systems
developed using nanomaterial-based sorbents
Nanomaterial-based sorbents have been primarily utilized
for preparation of three types of medically useful radionuclide generators, namely, 99Mo/99mTc, 68Ge/68Ga and
W/188Re generators. The characteristics of five nanomaterial-based sorbents, namely, polymer embedded
nanocrystalline titania (TiP), mixed phase nano-zirconia
(nano-ZrO2), tetragonal nano-zirconia (t-ZrO2), nanocrystalline alumina (c-Al2O3) and nano-ceria–polyacrylonitrile
composite (CeO2–PAN) were evaluated for use in the
preparation of the radionuclide generators [33–45]. The
methods of synthesis and structural characteristics of these
nanosorbents and their applicability towards preparation of
a particular type of radionuclide generator are briefly
summarized in Table 2. The development of different types
of radionuclide generators using nanosorbents is briefly
described below.
Mo/99mTc generator
The 99Mo/99mTc generators are extensively used for
assessing 99mTc which is the ‘work-horse’ of diagnostic
nuclear medicine [9, 46–49]. Every year, more than 30
million patient studies are performed worldwide using
Tc-based radiopharmaceuticals [9]. The most commonly used approach for assessing 99mTc from 99Mo is
based on the use of column chromatography using acidic
alumina as the sorbent matrix. However, the limited sorption capacity of bulk alumina (2–20 mg Mo/g) necessitates
the use of high specific activity 99Mo produced through
fission route [50]. The current production capability of
fission 99Mo is confined to a limited number of aging
nuclear reactors around the world, which have demonstrated numerous tribulations in the recent times [51–58].
Additionally, these reactors use highly enriched uranium
targets (HEU) for production of 99Mo and currently there is
an increasing global consensus to abandon the use of such
weapons grade target materials for medical radioisotope
production to thwart proliferation risks [51–58]. The supply chain of 99Mo is rather fragile and disruption in supply
of this radioisotope might adversely affect the patient services in different parts of the world [51–58]. In order to
reduce reliance on fission 99Mo, a number of alternative
strategies for 99Mo production, such as aqueous homogeneous reactor concept, target fuel isotope reactor concept,
direct cyclotron production of 99mTc, photo fission of 238U,
photon-induced transmutation of 100Mo and accelerator
driven subcritical assembly, have been proposed in the
recent past [59]. However, completing the technology
development and establishing the economics of these
approaches as new potential sources of 99Mo for clinical
applications will require several years. These approaches
are balanced on a fine line, with technical breakthroughs on
the one hand and long-term economic viability on the
other. Devising an effective strategy from the conversion of
HEU–LEU targets for 99Mo producers is challenging
owing to concerns about logistical difficulties and economics. A more prudent and time-tested approach which is
within the reach of most institutions having operating
research reactors in the world, is to use 99Mo produced by
(n,c) route for preparation of 99Mo/99mTc generators [56,
60, 61]. However, the relatively low specific activity
[0.35–3.5 Ci/g (13–130 GBq/g)] of (n,c)99Mo is the major
impediment for its utilization in the existing alumina based
J Radioanal Nucl Chem (2014) 299:741–757
generators, as large quantity of alumina would be required
which in turn would result in elution of 99mTc with low
RAC. Though several high capacity sorbents, such as
hydrous manganese dioxide, hydrous titanium dioxide,
hydrotalcite, cerium oxide, hydroxyapatite, polymeric zirconium compound (PZC), polytitanium oxychloride, alumina functionalized with a sulfate moiety, etc. have been
proposed to circumvent this limitation for preparation of
Mo/99mTc column generators [62–69], the inherent
drawbacks of these sorbent include loading of radioactive
Mo solution into the sorbent by batch process, difficulties
in realizing optimum capacity owing to slow kinetics of
sorption and requirement of a post purification column to
achieve requisite 99mTc purity and RAC.
In this context, the utility of nanomaterial-based sorbents which do not constitute a radical break with current
generator technology, has been the centre of much effort in
the quest for sorbents with enhanced capacity as well as
selectivity. In order to tap the potential of nanomaterials as
a sorbent for the preparation of clinical-scale 99Mo/99mTc
generators, the utility of TiP, t-ZrO2 and c-Al2O3 have not
only been profusely explored but also the feasibility of
making of 99Mo/99mTc generators using (n,c)99Mo has
been demonstrated [33, 36, 41, 44]. The 99Mo/99mTc generators developed using these sorbents and their performance characteristics are summarized in Table 3. It is seen
from the result that the adsorption capacity of this class of
sorbent are several fold greater than alumina and all these
nanosorbents are suitable for preparation of 99Mo/99mTc
generators for biomedical applications. During the process
demonstration step, it was observed that the 99mTc elution
yields were appreciably high and the level of RN, RC and
chemical impurities in 99mTc obtained from all these generators were well within the acceptable limits prescribed in
the pharmacopoeias [70].
As might have been expected, for all the sorbents, the
sorption capacity under dynamic conditions was much less
than that under equilibrium (static) conditions. This might
be attributed to mass transfer limitations, such as incomplete external film diffusion and/or intra-particle transfer
and slow kinetics of sorption. In view of the difficulties in
handling of radioactive material and to reduce the radiation
exposure, loading of 99Mo solution under dynamic (column-flow) condition seems to be an appealing protocol for
the preparation of chromatographic generators despite the
lower attainable sorption capacity and therefore recommended. Among the three sorbents studied, the use cAl2O3 provides the scope for the preparation of clinicalscale generator for routine use in nuclear medicine
departments owing to highest dynamic sorption capacity.
For the preparation of the generators, the authors have
utilized low specific activity 99Mo (*18.5 GBq/g) produced by neutron irradiation of natural MoO3 target in a
J Radioanal Nucl Chem (2014) 299:741–757
Table 3 Summary of
Mo/99mTc generators developed using nanosorbents
(mg Mo/g)
Activity of
Mo loaded
GBq (mCi)
yield of
Tc (%)
Maximum radioactive
concentration of 99mTc
achieved GBq (mCi)/mL
Level of 99Mo
impurity in
Tc (%)
purity of
4 (%)
Consistency in
3.74 (100)
0.74 (20)
Consistent for at
least 7 days
9.25 (250)
1.85 (50)
13.0 (350)
2.59 (70)
Consistent for at
least 10 days
Consistent for at
least 10 days
medium flux reactor (u * 1 9 1014 neutrons/cm2/s) for
1 week [33, 36]. Using c-Al2O3, 99Mo/99mTc generators of
activity up to 13 GBq (350 mCi) have been reported,
which is appreciably high for routine clinical use in hospital radiopharmacies. Using the same sorbent, it should be
possible to make column generators of [65 GBq (1.75 Ci)
by producing the 99Mo in reactors with [5 9 1014 neutrons/cm2/s as is the case with the Missouri University
Research Reactor in USA. The capacity of the generator
could be increased to *130 GBq (3.5 Ci) by using a
reactor having a neutron flux of 1 9 1015 neutrons/cm2/s
such as the Oak Ridge National Laboratory (ORNL)
reactor in USA or the SM Reactor at Dmitrovgrad in the
Russian Federation.
Recently, with a view to realize the scope of developing
clinical scale 99Mo/99mTc generator using (n,c)99Mo produced in medium flux reactors, a novel tandem column
generator concept was proposed [71]. This approach utilized two generator columns containing mesoporous alumina loaded with 99Mo, connected in series. The same
eluent (0.9 % NaCl solution) was used for elution for both
the columns. The major advantages of this approach over
conventional single column generators are (a) higher elution yield of 99mTc and (b) sharper elution profile resulting
in higher RAC of 99mTc eluate.
The use of enriched 98Mo would be a positive step
because target enrichment of C96 % augments the production yield and the specific activity of 99Mo by a factor
of *4. In view of the precious nature of enriched 98Mo, the
viability of recovering and reusing the enriched 98Mo from
the spent generator columns merits attention. It is pertinent
to point out that more than 80 % of Mo could be desorbed
from the spent generators prepared from this class of sorbent with 5 M NaOH solution containing H2O2 (15 mL of
5 M NaOH solution ? 1 mL of 30 % H2O2; [33, 36]).
One important point to note is that irrespective of the
specific activity of 99Mo used, the 99mTc is always NCA
and has essentially the same specific activity. The suitability of 99mTcO
4 eluate obtained from these generators in
preparation of standard 99mTc labeled formulations were
evaluated and the complexation yields of the radiolabeled
complexes were estimated to be [98 %, in all the cases.
The nanosorbents were stable to radiation and the
Mo/99mTc generators demonstrate satisfactory performance for [ 7 days, which is normally the shelf-life of
Mo/99mTc generators.
An examination of the utility nanomaterial-based sorbent in the development of 99Mo/99mTc generators clearly
indicates the impact of nanotechnology. This strategy
deserves greater attention not only because a greater range
of 99Mo/99mTc generators can be produced, but also for the
adaptability to use 99Mo produced by (n,c) route with a
wide range of specific activities. The concept of preparing
nanomaterial-based 99Mo/99mTc generators is inexpensive,
realistic, can be implemented in a very short period of time
and capable of producing pharmaceutical grade 99mTc to a
reasonable extent.
The IAEA [72] data base provides a summary of
approximately 251 research reactors currently operate
worldwide; of these, approximately 134 have sufficient
thermal neutron flux, target volume, and operational
capabilities for routine production of (n,c)99Mo. Fifty of
these research reactors have thermal neutron flux
[1 9 1014 neutrons/cm2/s, and the thermal flux of an
additional 85 reactors ranges from 1 9 1012 to 1 9 1014
neutrons/cm2/s. Seventy-eight of the above reactors are
already involved in radioisotope production, and these
reactors have a good geographic distribution. Many of
these reactors could be used for production of (n,c)99Mo.
A country that acquires 99Mo production as well as
Mo/99mTc generators fabrication capability will be better
able to meet its domestic needs and may have a quantity
for export. To ensure that all countries are well served, it
is advantageous to spread 99Mo/99mTc generators production facilities throughout the world. The more widely
the facilities are distributed, the more effectively used will
be the 99Mo/99mTc generators because losses from decay
will be diminished.
J Radioanal Nucl Chem (2014) 299:741–757
W-sorption capacity compared to alumina. More recently,
several sorbents with higher capacity for W such as gel–
metal oxide composite, synthetic alumina, polymeric titanium oxychloride and PZC, have been developed and
exploited for the preparation of 188W/188Re generators
[92–98]. However, the 188W/188Re generators prepared
using these sorbents could only be loaded under static
conditions, which is not preferred due to the difficulty in
handling the long-lived 188W (t1/2 = 69 days), radiation
exposure and expected deteriorating performance of the
generator when eluted under dynamic conditions. All
these generators demonstrated significant breakthrough of
W in 188Re and required a secondary column for
purification of the eluate.
At the intersection of column chromatography technique and nanomaterial-based sorbents lays a thriving
world of possibilities which is beneficial to the advancement of existing or pave the way for the exploration and
development of new 188W/188Re generators [33].
Undoubtedly, the impetus for the use of nanomaterialbased sorbents has come mainly from their potential to
realize high adsorption capacity resulting from the nanoscale dimensions, as a way to circumvent the limited
specific activity of 188W. The ability of three nanomaterialbased sorbents including TiP, t-ZrO2 and c-Al2O3 have
been comprehensively studied and profusely explored for
the development of 188W/188Re generators [33, 38, 42, 43],
the results of which are summarized in Table 4. Taking
advantage of the new physical properties uniquely associated with nanomaterials, 188W/188Re generators were
prepared using 88W produced in high flux reactors (/
* 1015 neutrons/cm2/s). A scrutiny of the results depicted
in Table 4 reveals that all these sorbents are suitable for
preparation of 188W/188Re generators and can easily be
scaled up to 37 GBq (1 Ci) activity level which is more
than adequate for routine clinical use. Among all, the cAl2O3 was found to exhibit the highest sorption capacity
under dynamic conditions as compared to TiP and t-ZrO2
and is therefore the most appropriate sorbent for the
preparation of clinical-scale 188W/188Re generator preparation. The performances of these generators were studied
for more than 6 months and reported to be satisfactory.
The 188Re elution yields were not only appreciably high
but also the level of RN, RC and chemical impurities in
Re obtained from all these generators were well within
the acceptable limits prescribed in the pharmacopoeias
[70]. In order to examine the suitability of 188ReO
obtained from the generators for radiolabeling studies, it
was complexed with standard ligands such as DMSA and
HEDP with [98 % RC purity.
Spurred by the perceived need to recycle the precious
enriched 186W target for subsequent irradiation, effective
W/188Re generator
The 188W/188Re generator using an acidic alumina column
is the most popular source for availing NCA 188Re suitable
for targeted radiotherapy [73]. The widespread interest in
use of 188Re in therapeutic nuclear medicine is due to its
reasonable half-life (16.9 h), high energy beta radiation
(Ebmax = 2.118 MeV), emission of a 155 keV c-ray (15 %)
suitable for imaging, potential availability in NCA form
from a generator, and chemistry similar to 99mTc which is
suitable for preparation of a wide variety of radiopharmaceuticals [74–85]. Despite such favorable attributes, 188Re
is not routinely used in therapeutic applications primarily
due to the unavailability of cost-effective 188W/188Re generators. Tungsten-188 can only be produced by double
neutron capture with low neutron absorption cross-sections
(r = 37.9 ± 0.6b),
(r = 64 ± 10b)] [86]. Further, due to the long half-life of
W (t1/2 = 69 days), relatively long irradiation periods are
required even for the production of 188W of modest specific
activity [86]. Consequently, 188W from the high flux reactors (/ * 1015 neutrons/cm2/s) such as the High Flux
Isotope Reactor in ORNL, USA or SM Reactor in Dmitrovgrad, Russian Federation or BR3 Reactor in Belgium can
only be used to make 188W/188Re generators suitable for
clinical use. The specific activity of 188W, produced in the
high flux reactors, ranges from 150 to 190 GBq/g of W [86].
While therapeutic applications of 188Re in nuclear
medicine ‘‘lives’’ at the interface between many disciplines, its dependence on 188W/188Re generator is considered to be one of the strongest. Due to the limited sorption
capacity of alumina (*50 mg W/g), 188Re obtained from
the alumina based 188W/188Re generators is of low RAC,
even while using 188W produced in high flux reactors for
preparation of the generators. Before undertaking the
preparation of 188Re radiopharmaceuticals, it is considered
appropriate to concentrate the generator eluate using suitable PEC technique [14, 17–21]. Often PEC of the 188Re
eluate results in a fairly complex system, addition of
chemical impurities, high dose rates and low reliability.
Recently, automated systems for the concentration of 188Re
eluate have also been developed [87]. However, the high
cost involved in the operation of the complex automation
systems, further increases the production cost of 188Re and
renders it cost-ineffective for routine therapeutic use. To
overcome these limitations, several alternate sorbents like
hydroxyapatite, the hydrous oxides of zirconium, titanium,
manganese, tin(IV), and cerium, silica gel, the AG 1-X12
and AG 50 W-X12 ion-exchange resins and activated
charcoal have been studied to determine their suitability for
the preparation of 188W/188Re generators [88–91]. Unfortunately, none of these materials exhibited an improved
J Radioanal Nucl Chem (2014) 299:741–757
Table 4 Summary of
W/188Re generators developed using nanosorbents
(mg W/g)
Activity of
W loaded
GBq (mCi)
yield of
Re (%)
Maximum radioactive
concentration of 188Re
achieved GBq (mCi)/mL
Level of 188W
impurity in
Re (%)
purity of
ReO4- (%)
Consistency in
1.85 (50)
0.37 (10)
Consistent for at
least 4 months
1.85 (50)
0.33 (9)
11.1 (300)
1.85 (50)
Consistent for at
least 6 months
Consistent for at
least 6 months
method has been developed to recover W from the spent
W/188Re generator column [33, 38, 42, 43]. This step is
equally important from the perspective of waste management point of view, as the exhausted generator columns
cannot be directly discarded without removing the sorbed
W from the column. More than 80 % of W could be
effectively desorbed from the spent generator columns by
passing 5 M NaOH solution containing H2O2 (15 mL of
5 M NaOH solution ? 1 mL of 30 % H2O2) through them
[33, 38, 42, 43].
There appears to be enticing interest among the user’s
community to consider the use of 188W/188Re generators
without the aid of PEC step. In this context, the scope of
using nanomaterial-based sorbent not only constitutes an
innovative concept but also pave the way for preparing
clinical scale 188W/188Re generators using high specific
activity (*150 GBq/g) 188W produced in high flux reactors akin to the convention alumina based 99Mo/99mTc
generators with fission 99Mo. Rhenium-188 obtained from
such 188W/188Re generators can provide the scope for
preparation of 188Re-based radiopharmaceuticals without
any post-elution purification or PEC requirement.
Although the scope for realizing clinical scale
W/188Re generators using 188W produced in high flux
reactors (1 9 1015 neutrons/cm2/s) without post elution set
up constitute as a step in the right direction, devising an
effective strategy to prepare generators using 188W
obtained from neutron irradiation of enriched (96 %) 186W
in medium flux (*1014 neutrons/cm2/s) research reactors
is challenging owing to the concerns about lower specific
activity of 188W. The specific activity of 188W from irradiation in medium flux reactors (1.5 GBq/g) would be far
lesser (*100 folds) than the product from high flux
(*1015 neutrons/cm2/s) reactors using same irradiation
time. This would have a profound influence on the amount
of sorbent required and in turn the size of the column to be
used. Therefore, only small-scale generators (of activity
*3.7 GBq) suitable for R&D purpose can be prepared
using low specific activity 188W and the present generation
of nanosorbents. The specific activity of 188W can be
augmented by enhancing the irradiation time. Irradiation of
enriched (*96 %) 186W targets for a longer time period
(*6 months) in medium neutron flux (*1014 neutrons/
cm2/s) reactors would result in the production of 188W of
specific activity *6.7 GBq/g [99]. With this specific
activity of 188W, it is possible to prepare 11 GBq
(300 mCi) 188W/188Re generators using 5–6 g of c-Al2O3,
which is quite reasonable for clinical use. Although this
strategy is technically challenging compared to the use of
high flux reactors research reactors, this alternative option
has merits due to the good distribution of medium flux
(*1014 neutrons/cm2/s) research reactors throughout the
world [72]. It would offer immediate benefits, with the
smallest practical hurdles for implementation.
While the use of nanomaterial-based sorbent unveiled
many possibilities in devising effective strategies to prepare 188W/188Re generators, the principal challenges for
widespread pursuit of this novel paradigm dependent upon
the production of 188W of appreciable specific activity in
medium neutron flux (*1014 neutrons/cm2/s) reactors.
This source of 188W is independent of existing supply
chains and would provide redundancy as well as emergency backup. Yet, the ultimate implementation of this
strategy in a country with operating medium neutron flux
research reactors purely relies on organizational preferences rather than technical considerations.
It is envisaged that the nanosorbents based 188W/188Re
generators (particularly c-Al2O3) will not replace existing
commercial alumina column chromatographic generators
(along with post processing set-up), and certainly not in the
near future, but will find a complementary role in ensuring
the availability of 188Re for therapeutic use.
Ge/68Ga generators
The 68Ge/68Ga generator has emerged as a convenient
source to provide 68Ga in a hospital radiopharmacy for
PET-based molecular imaging. The introduction of 68Ga
into clinical practice provided a significant breakthrough in
the ongoing developments in functional and metabolic
imaging using PET, which is independent of the availability of a cyclotron [100, 101]. Gallium-68 decays by
positron emission (89 %) having a maximum energy
1.92 MeV with a short half-life of 68 min, which is compatible with the pharmacokinetics of many peptides and
other small molecules [102]. The impressive success of
Ga-labeled peptides, namely 68Ga-DOTATOC, 68GaDOTATATE, and 68Ga-DOTANOC, paved the way not
only towards clinical acceptance of this particular tracer for
PET imaging of neuroendocrine tumors, but to the realization of the great potential of the 68Ge/68Ga generator for
modern nuclear medicine in general. Beside DOTAoctreotide derivatives, a large number of 68Ga-labeled
molecules have been developed and many others are used
in pre-clinical studies [103, 104]. Myocardial perfusion,
pulmonal blood flow, bone imaging, or membrane receptor
status can be expected to be observable with sophisticated
Ga-PET analogues [100–104].
Though the 68Ge/68Ga radionuclide generators have
been the object of development and investigation for
almost 50 years, their proper and relevant clinical use has
started only recently [6, 105, 106], due to lack of proper
sorbents, as one of the reasons. The past few years have
witnessed unprecedented endeavors by both academia and
the industry for developing a wide variety of 68Ge/68Ga
using a wide variety of sorbents such as Al2O3, CeO2,
SnO2, TiO2, ZrO2 and organic matrices in attempts to
obtain ionic 68Ga [105]. The 68Ge/68Ga generator technology has undergone several stages of modification and
sophistication and presently, these generators are supplied
by three commercial manufacturers, namely, Cyclotron
Ltd., Obninsk, Russian Federation, the Eckert and Ziegler
Isotope Products (EZIPs) and iThemba, Republic of South
Africa [107–110]. For preparation of 68Ge/68Ga generators,
the Cyclotron Ltd. uses a modified TiO2 phase [107], the
EZIPs uses titanium dioxide (IGG 100 [108]) and iThemba,
Republic of South Africa, uses a SnO2 [109, 110]. While
the commercial availability of a range of 68Ge/68Ga generators constitute a step in the right direction for providing
ionic 68Ga for PET, the low RAC, high acidity, unacceptable 68Ge breakthrough, and the presence of potential metal
ion impurities in the generator eluate have emerged as the
major deterrents in the path of direct preparation of 68Ga
based radiopharmaceuticals [105]. Also, most of the commercially available generators demonstrate deteriorating
performance in terms of increased 68Ge breakthrough and
reduced 68Ga elution yield on repeated elutions over a
prolonged period of time [105].
In order to circumvent these issues, attempts were made
to perform post-elution processing of 68Ga eluate from the
Ge/68Ga generator and a number of purification strategies
J Radioanal Nucl Chem (2014) 299:741–757
using anion and cation exchange chromatography and
fractionation have evolved which provide 68Ga in acceptable pH free from metallic impurities as well as 68Ge
breakthrough [105, 111–115]. However, these additional
manipulations not only make the studies with 68Ga more
time consuming which results in decay-loss of this shortlived radioisotope but also quite expensive.
It is pertinent to point out that 68Ge/68Ga generator must
be accepted not just as a good science but also to ensure
that quality of the 68Ga3? ion obtained from the generator
is amenable for the routine direct radiolabeling of a gamut
of pharmaceutical compounds at high specific activity and
RC purity for clinical purposes. While the utilization of
automatic post-elution purification as well as concentration
systems [116] has tangible benefits, use of 68Ge/68Ga
generators which could be directly used for the synthesis of
Ga radiotracers in the hospital radiopharmacy is a trustworthy proposition. The basis for the success of 68Ga radiopharmacy lies in the development of 68Ge/68Ga
generators systems providing the 68Ga not only in ionic
form but also in an acceptable RAC free from 68Ge
breakthrough as well as of potential metal ion impurities.
Recently, efforts were resorted towards preparation of
Ge/68Ga generators using nanomaterial-based sorbents
which can be directly used in the hospital radiopharmacy
similar to 99Mo/99mTc generators and considerable success
has been achieved in this direction [33]. Two nanosorbents, namely, t-ZrO2 and CeO2–PAN have been utilized
for preparation of the 68Ge/68Ga generators (each of
740 MBq activity; [33, 35, 39, 40]) and the results are
summarized in Table 5. Since, preparation of a single
patient-dose of 68Ga-radiopharmaceuticals that are commonly used in nuclear medicine departments requires
*74–185 MBq (2–5 mCi) of 68Ga activity, a 740 MBq
(20 mCi) generator would be adequate for regular clinical
use in a medium-scale hospital radiopharmacy. It can be
seen from the table that the sorption capacity of t-ZrO2 is
much higher than that of CeO2–PAN. Since 68Ge is
available in NCA form, 500 mg of either of these sorbents
would be adequate for preparation of 18.5 GBq (500 mCi)
Ge/68Ga generator. The performance of both these generators were evaluated for 1 year in terms of 68Ga yield,
Ge breakthrough, RAC of the 68Ga solution and suitability of the 68Ga for the preparation of 68Ga-labeled radiotracers. The elution yields of 68Ga from these
generators varied between 70 and 85 % and the breakthrough of 68Ge in 68Ga eluate was negligibly low
(\10-4 %). The presence of metal ion impurities such as
Fe3?, Cu2?, Al3?, Zn2?, Sn2?, Ti4?, Mn2?, etc., in 68Ga
eluate was negligibly low (\0.1 ppm) as determined by
ICP-AES analysis. Gallium-68 obtained from these generators could directly be utilized for preparation of various
radiopharmaceuticals with high radiolabeling yield
J Radioanal Nucl Chem (2014) 299:741–757
Table 5 Summary of
Ge/68Ga generators developed using nanosorbents
yield of
Maximum radioactive
concentration of 68Ga
achieved GBq (mCi)/
Level of
impurity in
Ga (%)
Level of chemical
impurities in 68Ga (%)
Activity of
GBq (mCi)
Consistency in
Sorption capacity
(mg Ge/g)
0.74 (20)
0.37 (10)
Ce4?, Fe3?, and Mn2? ions
were \1 lg/mL. No other
metal ion impurity
Consistent for
at least 1
0.74 (20)
0.44 (12)
Co2?, Cu2?, Cd2?, Ni2?
ions, etc., were \5 ng/mL.
No other metal ion
impurity detected
Consistent for
at least 1
([98 %) and appreciably high specific activity of the
radiolabeled conjugates. The performance of both these
generators remained consistent over the period of 1 year.
It is anticipated that the realization of this paradigmchanging approach for preparation of 68Ge/68Ga generator
would represent a cost-effective proposition for assessing
Ga to meet future research and clinical demands. The
availability of such reliable and easy-to-handle 68Ge/68Ga
generators would facilitate more research on new 68Ga
radiopharmaceuticals for PET imaging. The generator
systems are amenable for automation which can be successfully used in hospital radiopharmacies. The nanosorbent based generators have got very high potential for use
in institutions, where commercial sources of PET radioisotopes are not readily available or are too expensive.
Summary and conclusions
This article highlights the importance of nanomaterialbased adsorbents in the development of radionuclide generators. Nanomaterial-based adsorbents have proven to be
effective in enhancing the performance of the column
chromatography radionuclide generators owing to novel
adsorption characteristics such as large surface area, reactive surface and high specificity. A review of the research
indicates that significant strides have been made in this
fascinating field of research. Although this class of adsorbent has been relatively less explored compared to conventional bulk material adsorbents, generators using
nanomaterial-based adsorbents is evolving, and essentially
represents a story of a technique awaiting technology
realization. The advances made so far are exciting and
there are no technical barriers for their adoption. With the
appropriate selection of suitable adsorbent and parent/
daughter radionuclide pair, it would be possible to envision
a future where a wide range of radionuclide generators,
commensurate with hospital radiopharmacy can be prepared to address the need of nuclear medicine community.
Despite the huge potential of nanomaterial-based
adsorbents as chromatographic supports, wide scale availability of the nanomaterial is one of the major challenges
which currently obstruct the path for their widespread
progress. Establishing cost effective large-scale production
method for a constant and reliable supply of this class of
adsorbents is an appealing vision for the ongoing efforts to
create a foundation as well as advancement. This would not
only ensure a sustained growth and future expansion but
would also empower future developments. This is the area
in which innovation is required and where significant novel
developments can be expected to occur in near future.
There is no doubt that in the near future, efforts will be
focused to unlock the secrets for undertaking sustainable
large-scale, cost-effective production of nanomaterialbased adsorbents.
As applications of nanomaterial-based adsorbents and
use of generator prepared from this class of adsorbent
increases, development of automated generators is crucial.
Automation offers several advantages, including reducing
the radiation exposure to personnel, minimize the probability of human errors, offering consistent generator performance, and provides an elution record. Such automation
strategies must be hastened to expand the scope as well to
revolutionize radionuclide generators technology.
It is clear that nanomaterial-based radionuclide generator is still in its infancy, has to grow more in terms of
productivity and utility. We have passed few roadblocks
but without doubt the end of the road stretches into the
distance and nanomaterial stonemasons are going to be
busy for the foreseeable future as there is plenty of room
for high level research. With continuous research efforts,
we have every reason to believe that huge steps forward
will be made during the coming decade.
While merging nanomaterial-based adsorbents and column chromatography separation technique unveil innovations in radionuclide generator technology, and made
substantial inroads, regulatory approval of generator produced radionuclide as an approved pharmaceutical
J Radioanal Nucl Chem (2014) 299:741–757
ingredient, would of course, be a prerequisite for clinical
use. However, we must not forget that nanomaterial-based
radionuclide generator is required to be customized to
local legislative, regulatory and institutional conditions. It
is the responsibility of all the stakeholders, including scientists, engineers, clinicians, radiopharmacists, hospitals,
industries and federal agencies to share a common platform not only to harness the immense potential of nanomaterial-based radionuclide generator but also to create
this technology a mainstream for hospital radiopharmacy
Acknowledgments Research at the Bhabha Atomic Research
Centre is part of the ongoing activities of the Department of Atomic
Energy, India and is fully supported by government funding. The
authors are grateful to Dr. Gursharan Singh, Associate Director,
Radiochemistry and Isotope Group (I), Bhabha Atomic Research
Centre for his valuable support to the isotope program.
Conflict of interest
financial interest.
The authors have declared no conflicting
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