Download Radiohalogens: Chemistry and Applications

Radiohalogens: Chemistry
and Applications
Michael Adam
RADIOCHEMISTRY
NUTS AND BOLTS II
SNM 2008
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Applications
Two main categories
z Imaging
z Therapy
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Applications
z With
the exception of Brachytherapy and
radioiodines, which localize in the thyroid
and thyroid-originating cancers, for most
practical purposes radiohalogens must be
coupled with biomolecules (small and large)
for imaging or therapy.
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Radiohalogen Nuclides
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Radiohalogen Production
Most are produced on a cyclotron but
some such as I125,131 are produced with a
reactor. For more information see Pagani
et al. Eur. J. Nucl. Med., 24, 1301, 1997.
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Properties
(t1/2 =110min, 97% β+, 0.635 MeV positron
energy)
75Br (t =97 min), 1.74 MeV positron energy,
1/2
71%.
76Br (t =16.2hr), 3.98 MeV energy, 54%.
1/2
122I (t =3.6min)
1/2
123I (t =13.2 hr), commercially available
1/2
124I (t =4.18 d), emission not ideal but long t
1/2
1/2
125I (t =60d), Auger emitter and long t
1/2
1/2
77Br (t =57 hr), unavailable and high energy γ
1/2
z 18F
z
z
z
z
z
z
z
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Radiohalogens for Imaging
z PET: 18F, 75Br, 76Br, 122I, 124I
z SPECT: 77Br, 123I,
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Choosing a Radiohalogen for
Imaging
z Physical
properties
z Half
life
z Availability
z Labelling chemistry
z In-vivo dose considerations
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Radiohalogen Labeling
Chemistry
(eg. F-)
z Electrophilic (eg. F2)
z Nucleophilic
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Nucleophilic Reactions
anionic forms of halogens such as F-,
Br-, or Iz Usually obtained directly from the cyclotron
and can be used to exchange, displace or
substitute other halogens or leaving groups.
z For 18F- this is the most common labeling
reaction.
z Uses
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Nuleophilic Examples
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Nucleophilic Labelling
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Nucleophilic Iodine Exchange
Labeling
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Nucleophilic Bromine Labeling
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Electrophilic Halogen Labeling
z Labeling
occurs with an electro-positive
form of the halogen (X+)
z For F-18 requires an O-18 oxygen gas target
and carrier F2 to produce 18F2.
z For Br and I these can be obtained in an
electropositive form by in-situ oxidation
from the anion with agents such as
Choramine-T, or Peracetic acid.
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Electrophilic Examples
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Electrophilic Labeling
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Electrophilic Iodine Labeling
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Electrophilic Bromine Labeling
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Properties for Therapy
z
z
z
z
z
Must cause ionization and break bonds.
Emit β-, β+, or Auger electron or α-particle
Most commonly use is 131I for thyroid cancer
(available, t1/2 8d, inexpensive but has high energy
γ’s.
125I (Auger emitter), high LET but long half life.
211At, α emitter, high LET but less stable bond to
carbon.
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Radiohalogens for Therapy
z 131I, 125I, 211At
z Most
studied is labelled monoclonal
Antibodies (mAbs).
z FDA approved 131I-mAb (Bexxar) for nonHodgkin’s Lymphoma.
z Receptor binding peptides (somatostatin,
bombesin, annexin etc.)
z Small molecules such as 131I-MIBG
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Radiohalogens for Therapy
z 125IUDR,
incorporates into DNA of rapidly
growing cancer cells.
z Radiohalogenated Steriods –therapy of
hormone dependent tumors.
z Radiohalogented Oligomers (DNA, RNA,
PNA) bind to mRNA and DNA in cells.
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In Vivo Stability has been a Problem
with 211At-labeled biomolecules
z
Direct labeling of proteins with electrophilic
211At species results in an unstable attachment
in vivo
z
A 2-step method for 211At labeling of
biomolecules was developed using metallated
aromatic and vinyl derivatives
z
Using 211At-labeled benzoates, slowly
metabolized biomolecules (e.g. mAbs) are
stable to in vivo deastatination but labeled
biomolecules undergoing more rapid
metabolism release free astatide
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Radiohalogen Labeling of mAbs
using Aryl Conjugates
Comments:
1. Halobenzoates are stable to in vivo deiodination
2. Stannylbenzoates can be used to incorporate several halogens
3. Labeling process is more difficult and results in lower
yields than direct radioiodinations
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Anionic Boron-Cage Moieties
Investigated for Radiohalogenations
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Direct At-211 Labeling of mAbs using
Borane Derivatives
S
H
N
HN
O
NH
O
O
H
N
O
O O
H
O
O
O
H
N
NH
O
N
H
O
NH
O
O
O
N
H
O
N
H
O
O
O
S
O
Protein
O
N
N
H
Protein
S
O
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Summary
z Radiohalogenated
Radiopharmaceuticals
are an important area of Nuclear Medicine
for imaging and therapy.
z With the success of FDG there is now the
infrastructure to develop other 18F agents
z Future growth dependent on radiohalogen
chemistry and labeling of biomolecules.
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Questions
1.
2.
3.
4.
5.
6.
List 4 radiohalogens
Name one reactor produced radiohalogen
Name the two most widely used radiohalogens in
imaging
Nucleophilic labeling uses what form of the
radiohalogen
Name two radiohalogens useful in therapy
What kind of decay emission is useful for
therapy.
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Answers
1.
2.
3.
4.
5.
6.
I-123, F-18, Br-75, At-211 (one from the
table on slide 4)
I-125, could be I-131 also
I-123, F-18
Anionic (negatively charged)
I-125, At-211
Beta, Alpha, Auger electron
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