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Journal ArticleDOI

A no-carrier-added 72Se/72As radionuclide generator based on distillation

01 Apr 2004-Radiochimica Acta (Oldenbourg)-Vol. 92, pp 245-249

Abstract: Arsenic-72 is a positron emitting isotope with promising properties for syntheses of 7 2 As-labelled radiopharmaceuticals for future application in positron emission tomography. This work describes the radiochemical separation of no-carrier-added 7 2 Se from cyclotron irradiated germanium targets and the development of a 7 2 Se/ 7 2 As radionuclide generator, avoiding the addition of any selenium carrier. Using a vertical quartz tube device, no-carrier-added 7 2 As is nearly quantitatively released from various chloride salt solutions containing 7 2 Se within 10 min at a temperature of 100°C in an HCl gas flow. The kinetics of the 7 2 Se/ 7 2 As isotope generator has been studied in relation to temperature, salt charge, and redox-stability. Under optimised conditions, 7 2 Se remains almost quantitatively (> 99.7%) in solution.
Topics: Radionuclide Generator (57%)

Summary (2 min read)

1. Introduction

  • 72As is a positron emitting arsenic isotope, with properties promising for possible application as72As-labelled radiopharmaceuticals.
  • 630 keV (7.9%), 1461 keV (1.1%) and others (< 0.5%), the long physical half-life of 26 hours may render72As as a PET radionuclide of choice for the quantitative imaging of biochemical and physiological processes with longer biological half-lives,e.g. immunoimaging and receptor mapping.
  • The radionuclide 72As can be produced directly at medium-energy cyclotronsvia the 72Ge(p, n), 72Ge(d, 2n), 69Ga(α, n), 71Ga(α, 3n), and 71Ga(3He, 2n) reactions.
  • Various ways for * Author for correspondence (E-mail: frank.roesch@uni-mainz.de).
  • Due to the presence of selenium carrier, the separation yields were less than 70%.

Radiochemical separation of 72Se

  • GeCl4 is removed from the solutionvia distillation in an N2 flow (10 ml/min), while conc.
  • The distilled GeCl4 is trapped in an ice-cooled flask, filled with 20% H2SO4 and precipitates as GeO2.
  • No-carrier-added 72Se as well as the already generated72As remain in the flask quantitatively.
  • The neutron-irradiated germanium and the neutron irradiated selenium are treated analogously.

Cyclic separation of nca 72As from nca 72Se

  • For constructing the present distillative radionuclide generator system, an apparatus was adopted which has been shown to be versatile and adequate for a variety of thermochromatographic and distillative separations of generator radionuclide pairs.
  • This apparatus, first developed to separate the positron emitter94mTc from the irradiated molybdenum oxide within 25 minutes [10], was subsequently improved and used more universally for separations of the sys- tems110Sn/110In, 186W/186Re,188W/188Re [11, 12].
  • The following chlorides were tested: KCl, LiCl, NaCl, AlCl3, CaCl2, NH4Cl, BaCl2 and hydrazine dihydrochloride.
  • As the volume of the loaded generator is a critical parameter, the salts have not been used in equimolar amounts, but with the same mass of 1.0 g. Hydrochloric acid is passed through the inlet into the apparatus with a variable flow rate of 20–120 ml/ in.
  • The generator glass tubes were placed at room temperature into the oil bath, which was subsequently heated up to a defined end-temperature [protocol (i)].

3. Results and discussion

  • Separation of 72Se and recovery of macroscopic Ge-targets.
  • The upper group shows Fig. 3. Kinetics of distillative72As separation depending on the temperature; protocol (i).
  • The effect of salt additives on the nca seperation of72Se fraction has been systematically studied using the follow- ing salts: KCl, NaCl, AlCl3, NH4Cl, CaCl2, BaCl2 and hy- drazine dihydrochloride.
  • Fig. 8 shows that the selenium breakthrough is very low within the first hour of the separation process.
  • Thus, a complete oxidation with aqua regia is recommended prior to subsequent generator utilisation.

4. Conclusion

  • A 72Se/72As radionuclide generator utilising a distillation concept has been optimised.
  • It could be automated for future A no-carrier-added72Se/72As radionuclide generator based on distillation 249 use as a biomedical generator.
  • Systematic chemical investigations on the labelling chemistry of no-carrier-added radioarsenic, however, are required prior to the application of72As labelled compounds.
  • Financial support by the Deutsche Forschungsgemeinschaft (DFG-Grant Ro 985/9) is gratefully acknowledged.
  • Acknowledgement is made to the crew of the research reactor BER-II at the Berlin Hahn Meitner-Institut in Berlin for irradiations.

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Radiochim. Acta 92, 245–249 (2004)
by Oldenbourg Wissenschaftsverlag, München
A no-carrier-added
72
Se/
72
As radionuclide generator based on
distillation
By M. Jennewein
1
,A.Schmidt
1
, A. F. Novgorodov
2
,S.M.Qaim
3
and F. Rösch
1
,
1
Institute for Nuclear Chemistry, Johannes Gutenberg University, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany
2
Joint Institute for Nuclear Research, Laboratory of Nuclear Problems, RUS-141980 Dubna, Russian Federation
3
Institut für Nuklearchemie, Forschungszentrum Jülich GmbH, D-52425 Jülich, Germany
Dedicated to the memory of Prof. Dr. Dr. h.c. Gerhard L. Stöcklin
(Received October 16, 2003; accepted in final form January 29, 2004)
As-72 / Se-72 / Radionuclide generator / Distillation
Summary. Arsenic-72 is a positron emitting isotope with
promising properties for syntheses of
72
As-labelled radio-
pharmaceuticals for future application in positron emission
tomography. This work describes the radiochemical separation
of no-carrier-added
72
Se from cyclotron irradiated germanium
targets and the development of a
72
Se/
72
As radionuclide gen-
erator, avoiding the addition of any selenium carrier. Using
a vertical quartz tube device, no-carrier-added
72
As is nearly
quantitatively released from various chloride salt solutions
containing
72
Se within 10 min at a temperature of 100
C
in an HCl gas flow. The kinetics of the
72
Se/
72
As isotope
generator has been studied in relation to temperature, salt
charge, and redox-stability. Under optimised conditions,
72
Se
remains almost quantitatively (> 99.7%) in solution.
1. Introduction
72
As is a positron emitting arsenic isotope, with properties
promising for possible application as
72
As-labelled radio-
pharmaceuticals. It has a positron emission rate of 88% with
E
β+max
= 2.5MeV and E
β+mean
= 1.0 MeV [1]. Although
the positron emission decay is accompanied by photons of
834 keV (79.5%), 630 keV (7.9%), 1461 keV (1.1%) and
others (< 0.5%), the long physical half-life of 26 hours may
render
72
As as a PET radionuclide of choice for the quanti-
tative imaging of biochemical and physiological processes
with longer biological half-lives, e.g. immunoimaging and
receptor mapping. In these cases, the half-life of
72
As may
meet the radiopharmacological requirements resulting from
the slower localization kinetics of the targeting vectors.
The versatile chemistry of arsenic would permit the ra-
diolabelling of a broad spectrum of potentially valuable
pharmaceuticals.
The radionuclide
72
As can be produced directly at
medium-energy cyclotrons via the
72
Ge(p, n),
72
Ge(d, 2n),
69
Ga(α, n),
71
Ga(α, 3n), and
71
Ga(
3
He, 2n) reactions. Indi-
rectly, it can be produced as a daughter radionuclide of the
relatively long-lived
72
Se (T
1/2
= 8.5 d). Various ways for
*
Author for correspondence (E-mail: frank.roesch@uni-mainz.de).
the production of
72
Se have been described but mainly in
the context of
73
Se production. Both deuteron- and proton-
induced reactions on arsenic, and α-and
3
He-induced reac-
tions on germanium have been investigated [24]. Alterna-
tively,
72
Se can be obtained via proton induced spallation of
RbBr [5] or other spallation processes.
Radionuclide generator systems play a key role in pro-
viding both diagnostic and therapeutic radioisotopes [6]
for various applications in nuclear medicine, oncology and
interventional cardiology. In particular, the application of
positron emission tomography (PET) at centres lacking a cy-
clotron to produce the necessary radionuclides depends on
the availability of biomedical PET radionuclide generators.
Fig. 1 illustrates the transient radionuclide generator ki-
netics for the system
72
Se/
72
As. The time where the daugh-
ter activity is maximum can be calculated to be 88.6h.How-
ever, already after 48 h, i.e. every second day, it is theoretic-
ally possible to elute around 70% of the maximum daughter
activity.
Fig. 1. Transient radionuclide generator kinetics for the system
72
Se/
72
As. A independent activity of the parent isotope; B growth
of cumulative parent and daughter activity in a pure parent fraction;
C growth of daughter activity in a pure parent fraction; D inde-
pendent decay of the separated pure daughter fraction at maximum of
generated activity.

246 M. Jennewein et al.
Several
72
Se/
72
As generator systems have been proposed
previously. Al-Kouraishi and Boswell [7] were able to ob-
tain
72
As from a coagulated form of carrier-added
72
Se on
a Dowex 50 column in 15 ml of water. Due to the presence of
selenium carrier, the separation yields were less than 70%.
Electrolytic generators with
72
Se deposited on Pt electrodes
as Cu
72
Se have been reported [8, 9]. Another process involv-
ing addition of selenium carrier in the form of selenic acid
uses the cyclic reduction of selenium to Se
and a separation
of
72
As by filtration with subsequent oxidative dissolution of
Se
using H
2
O
2
prior to each separation cycle [5].
The aim of this work was to develop a
72
Se/
72
As gen-
erator without any addition of selenium carrier. The system
should be reliable for the routine separation of
72
As to allow
investigations on syntheses of
72
As-labelled radiopharma-
ceuticals and their evaluation.
2. Materials and methods
Isotope production
72
Se was produced at the compact cyclotron CV28 of the
Forschungszentrum Juelich via the (
3
He, 3n) nuclear re-
action on natural germanium. Irradiation was done with
36 MeV
3
He-particles at a beam current of 5 µA for 12 h,
giving a yield of about 185 MBq (5 mCi). To simulate the
behaviour of
72
Se,
75
Se was used in some experiments,
which was produced in a carrier-added (ca) form of spe-
cific activity 0.52 GBq/µmol via the (n)-reaction in the
nuclear research reactor BERII at the HMI Berlin (Φ =
4.0× 10
14
n/cm
2
s).
Analogously, to simulate the behaviour of no-carrier-
added (nca)
72
As,
77
As was used, which was produced
in a nca state via the
76
Ge(n)
77
Ge (T
1/2
= 11.30 h)
77
As (T
1/2
= 1.618 d) reaction on natural germanium at the
TRIGA reactor of the Institute of Nuclear Chemistry of the
University of Mainz (Φ = 4.0× 10
12
n/cm
2
s).
Radiochemical separation of
72
Se
To isolate
72
Se, the irradiated 100 mg germanium targets are
dissolved in 5 ml aqua regia and transferred to a two-necked
flask. GeCl
4
is removed from the solution via distillation in
an N
2
flow (10 ml/min), while conc. HCl is added contin-
uously (10 drops per minute) at a temperature of 130
C.
The distilled GeCl
4
is trapped in an ice-cooled flask, filled
with 20% H
2
SO
4
and precipitates as GeO
2
. No-carrier-added
72
Se as well as the already generated
72
As remain in the
flask quantitatively. The neutron-irradiated germanium and
the neutron irradiated selenium are treated analogously.
Cyclic separation of nca
72
As from nca
72
Se
For constructing the present distillative radionuclide gen-
erator system, an apparatus was adopted which has been
shown to be versatile and adequate for a variety of ther-
mochromatographic and distillative separations of generator
radionuclide pairs. This apparatus, first developed to sepa-
rate the positron emitter
94m
Tc from the irradiated molyb-
denum oxide within 25 minutes [10], was subsequently im-
proved and used more universally for separations of the sys-
Fig. 2. Sketch of the
72
Se/
72
As radionuclide generator apparatus. 1
outer quartz or glass tube; 2 inlet of HCl; 3 HCl vessel; 4 inner
quartz or glass tube; 5 ground joint; 6 open lower end of the inner
tube; 7
72
Se fraction; 8 upper end of the inner tube; 9 adsorber;
10 heating device, lead shielding.
tems
110
Sn/
110
In,
186
W/
186
Re,
188
W/
188
Re [11,12]. For a re-
cent review on thermochromatographic separations cf. [13].
The 5 ml HCl solution containing
72
Se is transferred to
a quartz or glass tube system as shown in Fig. 2, which is
inserted vertically into a heated oil-bath. 1.0 g of a chloride
salt and 1.0 ml of conc. HCl are added. The following chlo-
rides were tested: KCl, LiCl, NaCl, AlCl
3
,CaCl
2
,NH
4
Cl,
BaCl
2
and hydrazine dihydrochloride. As the volume of the
loaded generator is a critical parameter, the salts have not
been used in equimolar amounts, but with the same mass
of 1.0 g. Hydrochloric acid is passed through the inlet into
the apparatus with a variable ow rate of 20120 ml/min.
The temperature at the position of the
72
Se fraction inside the
tubecanberaisedupto140
C. The
72
As is volatilised as
AsCl
3
and transported with the stream of hydrochloric acid.
It is adsorbed on a cartridge, containing a suitable material
(e.g. charcoal). To determine HCl ow rates, the charcoal
cartridge was substituted by a 100 ml glass-syringe.
Two types of experimental setups have been used to
record the distillation kinetics of nca radioarsenic trichlo-
ride (
72
AsCl
3
and
77
AsCl
3
). The generator glass tubes were
placed at room temperature into the oil bath, which was
subsequently heated up to a defined end-temperature [pro-
tocol (i)]. The radioarsenic content in the containment was
measured on-line via γ -ray spectroscopy. For this purpose,
a NaI-detector was integrated into the lead shielding, with
the detector head close to the lower end of the genera-
tor. Alternatively, the generator glass tubes were placed in

A no-carrier-added
72
Se/
72
As radionuclide generator based on distillation 247
a pre-heated oil-bath [protocol (ii)] at an already defined
constant temperature and the distillation kinetics were meas-
ured analogously to protocol (i).
3. Results and discussion
Separation of
72
Se and recovery of macroscopic
Ge-targets
The radiochemical procedure used to separate nca
72
Se (or
nca
77
As) from irradiated natural germanium targets is based
on the formation of volatile GeCl
4
which is distilled at tem-
peratures above 130
C and precipitates in cold 20% H
2
SO
4
as GeO
2
. During this procedure the nca radioselenium exists
in a non-volatile oxidation state. The overall radiochemical
yield of nca
72
Se is 90± 4%. The germanium content of the
residue is less than 1%. The
77
Ge/
77
As separation was per-
formed analogously with comparable
77
As yields.
72
Se/
72
As generator
The concept of the
72
Se/
72
As isotope generator is based
on the high volatility of AsCl
3
formed at temperatures
above 80
C in the presence of chloride salts and HCl gas
(AsCl
3
b
p
= 130
C), while selenium remains in the residue
as a non-volatile complex. The selenium chloride Se
2
Cl
2
(b
p
= 130
C; decomposition), having a boiling point similar
to AsCl
3
is not formed under those experimental conditions.
The thermal volatility of SeCl
4
(b
p
= 191
C; sublimation
and almost complete dissociation to lower chlorides and
chlorine in the vapour) and of oxochloride SeOCl
2
(b
p
=
177
C) is low at temperatures below 120
C. However, the
stoichiometry of those selenium species might be affected
by the chloride salts cations. Hexachloroselenates of type
M
2
SeCl
6
are known for alkali chloride salts or for other
cations and compounds such as SeCl
4
·AlCl
3
, cf. Fig. 7 [14].
Fig. 3 shows the results observed while using the experi-
mental set-up described in protocol (i). The lower group of
plots shows the increase of
72
As in the absorber at increasing
temperatures from 110
C to 140
C. The upper group shows
Fig. 3. Kinetics of distillative
72
As separation depending on the tem-
perature; protocol (i). The lower group of graphs shows the increase
of
72
As in the absorber (9), the upper group shows the temperature
profiles in the generator flask.
the temperature profiles in the generator flask for the corres-
ponding end temperatures from 110 to 140
C. The highest
yield observed is 60% after 30 min at 140
C. At lower tem-
peratures, such as 110
C, only 20% yield of separated
72
As
is achievable after 40 min. This procedure can be repeated
as soon as no-carrier-added
72
As is formed again (see also
Fig. 1).
The advantage of the experimental set-up described in
protocol (ii) is a significantly reduced distillation time ne-
cessary to separate the nca radioarsenic. Fig. 4 shows the
results of the kinetic measurements, performed as described
in protocol (ii). At a temperature of 140
C, > 98% yield was
achieved already after 7 minutes. In terms of the retention of
the nca radioselenium generator charge, it is, however, ne-
cessary to compromise between generator running time and
temperature. At a temperature of 80
C, the maximum yield
of
72
As of about 95% was reached after only 17 minutes, and
the kinetics obviously are much slower than at higher tem-
peratures. Fig. 5 shows the time needed for 50% and 100%
72
As separation yield at different temperatures. A tempera-
ture of 105
C seems to be optimum which is the inflection
Fig. 4. Distillation kinetics of
77
AsCl
3
; protocol (ii). T = 80, 110 and
140
C, HCl flow rate = 60 ml/min.
Fig. 5. Determination of optimum distillation temperature of the
72
Se/
72
As radionuclide generator for 100%
72
As separation yield (a)
and for 50%
72
As separation yield (b).

248 M. Jennewein et al.
point (zero point in the second derivative) of the graphs
shown in Fig. 5.
The influence of the HCl ow rate on the distillation ki-
netics of
77
AsCl
3
was studied in more detail, as illustrated
in Fig. 6. A tripling of the HCl flow rate is followed by an
approximate tripling in the nca radioarsenic volatilization
at t = 10 min. At a lower flow rate of 20 ml/min the
72
As
separation yield of 100% cannot be achieved. A maximum
of 80% yield is achieved after 40 minutes distillation time.
Consequently, a constant HCl flow rate of 60 ml/min was
adjusted for routine use. This indicates the importance of
a reproducible maintenance of the HCl flow. This is, how-
ever, a technical problem, because of the fast and severe
oxidation of the pressure reducer at the gas cylinder outlet
valve.
The effect of salt additives on the nca seperation of
72
Se
fraction has been systematically studied using the follow-
ing salts: KCl, NaCl, AlCl
3
,NH
4
Cl, CaCl
2
,BaCl
2
and hy-
drazine dihydrochloride. The results are illustrated in Fig. 7.
Although usage of equimolar amounts of different salts
seemed to be quite adequate, this was not possible because
of the fixed volume of the generator apparatus, resulting in
a constant volume of liquid solution in which an equimo-
lar amount of salt e.g. AlCl
3
, would have not been solu-
ble. Therefore, we used 1 g of compound per salt tested.
The different chlorides were used to vary the chlorine ion
Fig. 6. Distillation kinetics of
77
AsCl
3
at different HCl flow rates, T =
90
C.
Fig. 7. Distillation kinetics of
72
AsCl
3
with varying salts in the genera-
tor charge, T = 100
C; HCl flow rate = 60 ml/min.
Fig. 8. Se-retention of the
72
Se/
72
As generator after re-oxidation, T =
80
C; HCl flow rate = 60 ml/min. The result shown here relates to the
small amount of
75
Se distilled over in a simulation experiment.
density in the solution, while hydrazine dihydrochloride was
used to observe whether the addition of a reducing agent
has an effect on the nca
72
AsCl
3
formation or not. The
amount of chlorine ions per ml generator charge varied
from 3.4 mmol for NaCl to 1.0 mmol for BaCl
2
. Obviously
this is not reflected in the measured results, where KCl
(2.7 mmol/ml generator charge) showed the best distillation
kinetics and NaCl the worst. A possible explanation for this
result is the lower solubility of NaCl compared to KCl in
hot HCl, which could be visibly observed, but is not de-
scribed in the literature. For routine use of the generator, KCl
is recommended.
On the contrary to nca radioarsenic, which is always
present as AsCl
3
under these reaction conditions, different
oxidation states seem to be possible for selenium, resulting
in significant differences in retention in the generator sys-
tem. Prior to transferring the radioselenium to the generator
apparatus, it was completely oxidised via refluxing for 2 h in
5 ml aqua regia. Fig. 8 shows that the selenium breakthrough
is very low within the first hour of the separation process.
The procedure is therefore good for the separation of nca ra-
dioarsenic. The selenium retention for suggested separation
periods of less than 10 minutes is > 99.9%.
A longer separation period will possibly result in the
reduction of selenium, yielding volatile radioselenium com-
pounds. This is indicated by an increase of the selenium
breakthrough at t > 60 min (see Fig. 8). Thus, a complete
oxidation with aqua regia is recommended prior to subse-
quent generator utilisation. When the generator was used
one day after the previous separation without pre-oxidation,
the selenium breakthrough was > 75% at a temperature of
80
C after 20 minutes of the separation process. This could
easily be avoided by adding 0.5 ml of concentrated HNO
3
prior to each generator run and heating the system up for
1 hour, before turning on the HCl gas flow.
4. Conclusion
A
72
Se/
72
As radionuclide generator utilising a distillation
concept has been optimised. It could be automated for future

A no-carrier-added
72
Se/
72
As radionuclide generator based on distillation 249
use as a biomedical generator. At an optimum temperature
of 105
C, more than 99% of the nca
72
As is separated in
less than 10 minutes at a nca
72
Se contamination level below
0.05%. Systematic chemical investigations on the labelling
chemistry of no-carrier-added radioarsenic, however, are re-
quired prior to the application of
72
As labelled compounds.
Acknowledgment. Financial support by the Deutsche Forschungsge-
meinschaft (DFG-Grant Ro 985/9) is gratefully acknowledged. Ac-
knowledgement is made to the crew of the research reactor BER-II at
the Berlin Hahn Meitner-Institut in Berlin for irradiations.
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Tapan K. Nayak, Martin W. Brechbiel1Institutions (1)
TL;DR: The opportunities and challenges of radioimmunoimaging with select longer-lived positron-emitting radionuclides such as (124)I, (89)Zr, and (86)Y with respect toRadionuclide production, ease of radiolabeling intact antibodies, imaging characteristics, radiation dosimetry, and clinical translation potential are examined.
Abstract: Radioimmunoimaging and therapy has been an area of interest for several decades. Steady progress has been made toward clinical translation of radiolabeled monoclonal antibodies for diagnosis and treatment of diseases. Tremendous advances have been made in imaging technologies such as positron emission tomography (PET). However, these advances have so far eluded routine translation into clinical radioimmunoimaging applications due to the mismatch between the short half-lives of routinely used positron-emitting radionuclides such as (18)F versus the pharmacokinetics of most intact monoclonal antibodies of interest. The lack of suitable positron-emitting radionuclides that match the pharmacokinetics of intact antibodies has generated interest in exploring the use of longer-lived positron emitters that are more suitable for radioimmunoimaging and dosimetry applications with intact monoclonal antibodies. In this review, we examine the opportunities and challenges of radioimmunoimaging with select longer-lived positron-emitting radionuclides such as (124)I, (89)Zr, and (86)Y with respect to radionuclide production, ease of radiolabeling intact antibodies, imaging characteristics, radiation dosimetry, and clinical translation potential.

152 citations


Journal ArticleDOI
TL;DR: The physical characteristics of 60 radionuclides, including β+, β−−, γ-ray, and α-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs are described.
Abstract: Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11C-, 13N-, 15O-, and 18F-radiopharmaceuticals for use with positron emission tomography (PET) and 99mTc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of "nonstandard" radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including beta+, beta-, gamma-ray, and alpha-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy gamma-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64Cu, 68Ga, 86Y, 89Zr, and 124I are discussed.

132 citations


Journal ArticleDOI
Marc Jennewein1, Marc Jennewein2, Matthew A. Lewis, Dawen Zhao3  +12 moreInstitutions (4)
TL;DR: Results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.
Abstract: Purpose: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. Experimental Design: Bavituximab was labeled with 74 As (h + ,T1/2 17.8 days) or 77 As (h - ,T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1tumors in rats. Results: Clear images of the tumors were obtained using planar g-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohisto- chemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.

100 citations


Journal ArticleDOI
TL;DR: Different approaches to labelling proteins with positron-emitting nuclides are discussed with suggestions made depending on the biological features of the tracer, emphasising chemical, biological and pharmacological considerations in labelling proteinaceous tracer applications.
Abstract: Background Dynamic biomedical research is currently yielding a wealth of information about disease-associated molecular alterations on cell surfaces and in the extracellular space. The ability to visualize and quantify these alterations in vivo could provide important diagnostic information and be used to guide individually-optimized therapy. Biotechnology can provide proteinaceous molecular probes with highly specific target recognitions. Suitably labelled, these may be used as tracers for radionuclide-based imaging of molecular disease signatures. If the labels are positron-emitting radionuclides, the superior resolution, sensitivity and quantification capability of positron emission tomography (PET) can be exploited. Scope of review This article discusses different approaches to labelling proteins with positron-emitting nuclides with suggestions made depending on the biological features of the tracers. Major conclusions Factors such as matching biological and physical half-lives, availability of the nuclide, labelling yields, and influences of labelling on targeting properties (affinity, charge and lipophilicity, cellular processing and retention of catabolites) should be considered when selecting a labelling strategy for each proteinaceous tracer. General significance The labelling strategy used can make all the difference between success and failure in a tracer application. This review emphasises chemical, biological and pharmacological considerations in labelling proteins with positron-emitting radionuclides.

86 citations


Cites background from "A no-carrier-added 72Se/72As radion..."

  • ...Radioarsenic can be separated from irradiated targets by distillation [338], solid-phase extraction [339], or dry distillation [340]....

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Journal ArticleDOI
Syed M. Qaim1Institutions (1)
Abstract: Abstract Medical radionuclide production technology is well established. Both reactors and cyclotrons are utilized for production; the positron emitters, however, are produced exclusively using cyclotrons. A brief survey of the production methods of most commonly used diagnostic and therapeutic radionuclides is given. The emerging radionuclides are considered in more detail. They comprise novel positron emitters and therapeutic radionuclides emitting low-range electrons and α-particles. The possible alternative production routes of a few established radionuclides, like 68Ga and 99mTc, are discussed. The status of standardisation of production data of the commonly used as well as of some emerging radionuclides is briefly mentioned. Some notions on anticipated future trends in the production and application of radionuclides are considered.

78 citations


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266 citations