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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.