• RADIOIODINE PRODUCTION
• LABELLING REACTION
• USES and APPLICATIONS
Paola Panichelli, Vancouver 08/09/2008
[124I]Iodine-β-CIT is a radiopharmaceutical injectable solution. [124I]β-CIT
belongs to a group of compounds derived from cocaine that bind to dopamine
transporters (TDA). The replacement of the ester link between tropane and
phenyl fraction in cocaine with a stable C-C gives rise to a higher metabolic
stabilization and enhance the affinity of union with the TDA.
(124I) is a radioactive isotope of iodine which is produced by the following nuclear reaction:
from 124TeO with an isotopic purity higher than 99.5%.
124I has a half-life of 4.176 days
(100.22 hours). 124I decays in stable
Tellurium [124Te] ( 100%) by an
emission of β+ (23%) with a
maximum energy of 0.603 MeV and
by an electronic capture (>98%)
according the decay scheme:
124I is produced on an 18
MeV IBA cyclotron using a
COSTIS (Compact Solid
Target Irradiation System)
solid target holder. COSTIS
is designed for irradiation
of solid materials.
IBA Cyclotron COSTIS Solid Target
Peculiarities of Compact Solid Target System
(COSTIS) Solid target:
-Allows the use any solid form (oxides, plated and
pressed powder compounds )
-Allows degrading of energy, for optimizing
radioisotope yield and minimizing impurities.
-Allows helium cooling for irradiation of low
-Allows the repeated use of target disks (in the case
of 124 I up to ten times).
COSTIS Solid Target - Allows remote handling of irradiated target disk.
Evaluation of the nuclear reaction best value of irradiation energy:
Beam energy has a cross section of 15.4 Mev maximum in order to reduce the
incident energy of protons and limit the production of 123I.
124Te(p,n)124I Cross Section 124Te(p,n)123I Cross Section
In this range of energy the time to limit 123I percentage to less than 5% is
about 84h; so we decided to set the time of application (TOA) of the mixture at
96h from the end of synthesis (EOS)
-The separation of radioiodine (124I) from the irradiated target occurs by
a thermo-distillation process.
-TERIMO is an automated module for thermo-chromatographic
separation of radionuclides :
• GMP compliant module
• Small footprint – fits into mini-hot
• Autonomous, PLC controlled
• Ethernet based PLC/SCADA
The apparatus for thermo-distillation separation of radioiodine (124I) from the
irradiated 124TeO2 possesses an holder in quartz for positioning of the disk, a
fast electric heater, a thermocouple for temperature measurements, an alumina
trap for adsorbing tellurium oxide vapours, and a quartz bulb containing the
The irradiated target is placed inside the quartz furnace of the synthesis
module TERIMO. It is heated up 780° C until it melts, and the radioiodine is
released as (124I2) gas and trapped in an absorption solution of NaOH 0.02M.
USES and APPLICATIONS:
Iodine-124(124 I) labeled compounds can be used with PET for
imaging and dosimetry of radioiodine treatments
The most interesting molecules in nuclear medicine labeled with
(124 I)Iodoßcit (124I)IodoDopa (124I)-PIB
COOCH3 COOH S
H NH2 NHCH3
The synthesis of [124I]-β-CIT consists of the following procedure:
2)C18 Sep Pack Lignt
[2β-carbomethoxy-3β-(4-trimethylstannylphenyl)tropane] [124I]Iodine-β-CIT ( 2β-carbomethoxy-3β-(4-iodiophenyl)-tropane
The first step of the synthesis is the iodination of the stannylated
precursor.Ortophosforic acid is used to make a mixture acid. Peracetic acid is used
to transforms the Iodide (I-) in Iodine (I2) for the electrophylic reaction.
Subsequently Iodine attacks the tin group of the precursor.
Sodium Bisolphite traps the iodine excess.
After Iodination, the compound is purified through a C-18 cartridge which is
washed with water and eluted with
an ethanolic solution at 95 %.
Product’s Specifications :
Specifications for radiopharmaceuticals should include:
EMEA/CHMP/QWP/306970/2007: Guideline on
•Radiochemical purity Radiopharmaceuticals
•Chemical purity European Pharmacopoeia 5.0 01/2005:0125:
Appearance: Clear colourless, free of particles solution
Radioactive concentration: the radioactivity of a radionuclide per unit volume
Radioconcentration is a specific typical control for a radiopharmaceutical,
to determine stability of strength, as well as uniformity of dosage units.
Radionuclidic Identity: a radionuclide can be identify by its mode of decay, its
half-life and the energy of its nuclear emission.
Characteristic peak of 124I decay scheme
Characteristic peaks of beta+ emitters
Half life of 124I
Radionuclidic purity: The ratio, expressed as a percentage, of the radioactivity
of the radionuclide concerned to the total radioactivity of the radiopharmaceutical
It is aimed at excluding those isotopes having characteristics similar to 124I, that,
if present in the product, would interfere with the emission spectrum and hence
with diagnostic imaging.
Radiochemical purity: the ratio expressed as a percentage of the radioactivity of
the radionuclide concerned which is present in the radiopharmaceutical
preparation in the stated chemical form, to the total radioactivity of that
radionuclide present in the radiopharmaceutical preparation.
Chemical purity: on radiopharmaceutical preparations chemical purity is
controlled by specifying limits on chemical impurities.
Radiochemical purity and Chemical purity and used to evaluate the presence
and the quantity of impurities..
Specific Radioactivity: the radioactivity of a radionuclide per unit mass of the
elements or of the chemical form concerned.
pH, Osmolality, Bacterial Endotoxins-Pyrogens, Sterility must be tested for all
products intended for parenteral use.
SPECIFICATIONS TEST LIMITS
Appearance Visual Inspection Clear; colorless solution free of particulates
Radioactive concentration Ionization chamber 13MBq/mL ± 10%
( at calibration time and date)
Radionuclidic identification Gamma Spectroscopy Energy of γ-ray Peak at 511 Kev and
Radionuclidic identification Gamma Spectroscopy Peak at 602.72 Kev / 1691.02 Kev/ 722.79Kev
Half-life Gamma Spectroscopy 4.18 days ±5%
Radionuclidic purity Gamma Spectroscopy ≥ 95 %
HPLC (test A) HPLC
[124I]-β-CIT ≥ 95 %
TLC (test B) TLC
[124I]-β-CIT ≥ 95 %
HPLC (test A)
[124I]-β-CIT HPLC ≤ ,2 µg/ml
SPECTROPHOTOMETRY UV/VIS (Test B) Spectrophotometer
Tellurium ≤ 1 µg/ml
Specific Radioactivity HPLC >107.3GBq/ml
pH potentiometric 5≤pH≤6
Residual Solvents GC
Ethanol ≤5 mg/ml
osmolality osmometer 260-320 mosm/kg
Bacterial Endotoxin LAL Ph.Eur ≤17.5 EU/mL
Sterility Ph.Eur sterile
SPC for AIC REGISTRATION
[124I]-β-CIT is a new radiopharmaceutical compound for
neurodegenerative disorder diagnosis with PET imaging.
It is an anologue of cocaine and binds to dopamine and serotonin
Neurodegenerative disorders, such as Parkinson’s disease, are
characterized by degeneration of dopaminergic neurons in the
substantia nigra, with loss of their nerve terminals in the basal
ganglia structure, especially in the striatum.
Phase III clinical trial, open label, non-randomized, single dose
Thirty Parkinson patients “de novo”
124I Beta CIT
Maximum injectable dose 18 MBq
Clinical Sites for patients recruitment
124I Beta CIT Dosimetry:
Polmone 0,1 0,8360656
Liver 0,09 0,7791045
Colon Descendig 0,05 0,4484536
Colon Ascending 0,05 0,425
Urinary bladder 0,03 0,26
Bowel 0,02 0,1670588
Surrenal 0,02 0,2057143
Pancreas 0,02 0,1605263
Bone 0,02 0,1308642
Ovarium 0,02 0,1612245
Kidney 0,01 0,0909091
Stomach 0,01 0,0826087
Marrow 0,01 0,062766
Speen 0,01 0,0828571
Breast 0,01 0,0928571
Thyroid 0,01 0,0980392
Testes 0,01 0,1072464
[124I]-β-CIT vs [123I]-β-CIT
With respect to [123I]-β-CIT, the most used radiotracer for SPECT (Single
Photon Emission Tomography) diagnosis of Parkinson disease, the
compund labeled with iodine-124 has several advantages in the diagnostic
1. the possibility of a reliable quantitative analysis of tracer kinetics, instead of
the semi-quantitative approach with iodine-123 in SPECT;
2. the possibility to follow over time tracer kinetics, thanks to the longer half life
of 124I (t1/2 :4.18 d) than 123 I (t1/2:13,27 h).
3. the better resolution of PET in comparison to SPECT.
USES and APPLICATIONS:
EXAMPLE OF PET IMAGING WITH [124I]-Β-CIT
Nowadays dopamine transporters 124 I-tracers
seem to be the best markers for identifying
Parkinson’s disease patients with high
sensitivity and specificity .
Dopamine transporter (DAT) imaging with
[124I]-β-CIT represents a new promising
diagnostical technique to evaluate dopamine
neuron loss, which is responsible for most of
the symptoms in Parkinson’s Disease patients.