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Amsterdam & O‐15 radiopharmaceuticals
Robert Schuit
Tracer H215O 13NH3
82Rb 18F-BMS
Half life
Production
Positron Range
Radiation
Image Quality
Quantitative
9.97 min
Cyclotron
0.4 mm
~ 1.0 mSv
+++
++
122 s
Cyclotron
1.1 mm
~ 0.5 mSv
++
++++
76 s
Generator
2.8 mm
~ 4.0 mSv
++
+
Knaapen et al, Clin Res Cardiol 2008
110 min
Cyclotron
0.4 mm
~ 4.0 mSv
++++
+++
‐First PET center in the Netherlands in Groningen (early 90’s).
‐Prof Adriaan Lammertsma from Hammersmith to Amsterdam.
Dedicated O‐15 cyclotron Continuous flow of O‐15 (steady state imaging) Easy modelling, no arterial line for input
‐Package deal with CTI (Siemens): HR+, HRRT and RDS111.
‐
Late 90’s – early 00’s
• No 14N (d, n)15O but 15N (p, n) 15O
Siemens idea of continiuous flow• Dual beam, unload every 67 seconds one target.
• Technical not possible in return C‐11 target system
• Alternative: bolus administration of O‐15 gasses.‐ setup the gas delivery to patient‐ setup the kinetic modelling
Logistics
• Departement on 5th floor, cyclotron at ‐2 (parking garage)
• 100 metre 1/16” PEEK tubing (unshielded) – 15O for [15O]water– 15O for [15O]O2
– 15O for [15O]CO– 15O for [15O]CO2
• push gas helium at 300 mL.min‐1
Chemistry [15O]water
• Siemens [15O]water module• Targetgas: 99% 15N2
/O2 (39/1)
30‐40 µA on target. Pressure 600 psi. COT 0.15 sec
Pd catalyzed conversion in oven at 250‐ flow: air = 115 sccm / hydrogen = 68 sccm
Yield: 2‐4 GBq [15O]water
Chemistry [15O]CO
• Siemens GPU• Oven at 975°
• 40 µA; COT 0.3 sec.• Yield 3-5 Bq
• CO2 path is converted in a spare CO path.
Quality controle – [15O]water
• Start of the day – test production• Product is sampled in a sterile vial.
– Microbiology– pH, color, endotoxines, osmolarity,– Waste vial Colony‐forming unit
Quality control 15O gas
Quality controle [15O]gas
• GC:RadionuclidePurity >97%
Half‐life
Gas delivery system (GDS)
GDS
GDS
To patient
Research patientcare
• Multiple project in neurology, oncology and cardiology.
• Neurology: Moya-Moya, cerebral ischemia, brain perfusion.
• Oncoly: tumor flow (correction of other ligand data)
• Cardiology: MBF,
Brain perfusion - cerebral ischemia
hybrid 15O-water positron emission tomography (PET)/computed tomography (CT)-based coronary angiography (CTCA) imaging for the evaluation of coronary artery disease (CAD)
CTCA followed by [15O]water baseline + [15O]water (stress)
MB F
MB F
4.0
0.0
0.0
1.0
In house developed Cardiac VUer Conclusion:Hybrid 15O-water PET/CTCA imaging impacts clinical decision-making with regard to referral for ICA and revascularization procedures.
Production of O-15 water
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Future plans
• 2017 – new building: Imaging Building
• Radiology + Nuclear Medicine
• 4 Cyclotrons, xMRI, xCT, 2 PETCT+PETMRI , laserlab• 2 IBA 18/8, 30MeV x + dedicated O-15
• Re-design O-15 production/logistics
Cyclon 3d Hidex
Deutrons vs proton accelaration
• DEUTRON (IBA cyclone 3dPro’sLow energy (3.4 MeV)Continuous flowCoffee machine (simple)Cheap target gasEasy logisticsBedside production of [15O]water
Con’sShielded transport linesSecure O-15 transport over multiple
PCT’s
• PROTON (RDS111)Pro’sWe use it routinely.Good separation production and patient
Con’sExpensieve targetgas/maintanceLogistics high workload
Explora vs Hidex• Pro’sSeparation production – patient
Syringe into loop, MEDRAD injection.High flow injection. Sharp input
function, optimol for modelling
15 year experience – results are good (production + microbiology)
• Con’sLow level of GMPlaborious
• Pro’sGMP level high
Bedside automated production -operated by camera people
In theory – straight forward
• Con’sNEWLow pressure limit – low injection flowSuboptimal modellingExpensieve cartridges
Hidex
Problems:
O-15 radiopharmaceuticals for patient care.
Cardiologist are interested no cyclotronHave cyclotrons hard to get the cardiologist
IBA cyclone 3d is not a standard product. only batch production
No other vendor of low energy deutron accelarator.