Jacqueline Roberts St James University Hospital

Leeds Teaching Hospitals NHS Trust

Calibration & Testing of an

Intego Automatic F-18

Dispensing & Injecting

System

R’nuclide Body dose - point source in air [mSv.m2/(GBq.h)]

Skin dose - contact with 5ml syringe [mSv/(MBq.h)]

Tc-99m 0.02168 0.354

F-18 0.1655 2.88

Ga-68 0.1580 31.4

I-124 0.1745 10.7

Y-90 0 43.5

NMed staff at greater risk of > 500mSv pa skin dose due to increased use of PET tracers & RNT. PET gives ~8x WB γ dose ct Tc99m, skin β+ dose 8 – 89 x greater. Intego > 20% lower wb dose, 95% lower extrem dose

Kemerink et al EJNMMI Mar 2012 39(3) 529-32 / ORAMED study 2011

Automate all or one of dispensing/injecting

Integrated systems do both – direct patient connection to dispensing system

Modular systems do this in separate parts

Different radiopharmacy requirements for both

Many varieties of design

System calibration requirements also differ

Internal calibrator checks & end-point dispensed activity checks needed

Difficulty depends on particular system design

MedRad/Bayer – Intego Integrated F18 Dispensing & Infusion System

Iride

System

Modular

Dispenser;

Injector

Tema Karl 100

Dispenser & Injector

Automated Dose

Dispenser

Automate all or one of dispensing/injecting

Integrated systems do both – direct patient connection to dispensing system

Modular systems do this in separate parts

Different radiopharmacy requirements for both

Many varieties of design

System calibration requirements also differ

Internal calibrator checks & end-point dispensed activity checks needed

Difficulty depends on particular system design

E.g. Modular unit that dispenses to a syringe – can cross-check syringe activity, applying geometrical/volume correction

E.g.2 Modular unit that dispenses in bespoke cartridge & measures with ‘calibrated’ W shield (Trasis)

E.g.3 Integrated unit that infuses direct to patient (Intego) – need to dispense into container & cross-check this with corrections

F18 Stock Vial

Precision Peristaltic Pump

Calibrator Well (Veenstra)

Waste Reservoir

Patient Line

Connection Point Saline Pump

Patient Infusion Line

Internal Tubing Set

Stock Vial

Shielded Pot

Needles for

F18 Stock Vial

Narrow

Gauge

Tube for

Precision

Pump

Fixed -

Geometry

Plastic Coil

(sits inside

calibrator)

Port

Valve to

Patient

Infusion

Line

Waste F18

Reservoir

Saline Input

from Pump

Setup Considerations Solution

Pharmacy Issues – Sterility of multiple dispensing with one internal tubing set

Local aseptic procedure agreed for r’pharm &

users

Accuracy Calibration Before First Use & Annually – Use 3.7MBq Co57 & Cs137 sealed sources

Achieved but used pen point source of Co57 Activ just about ok

Linearity Check – Before first use & then quarterly

Passed- 5GBq F18 left overnight, auto program

Daily QC incl Constancy Source Used Cs137 source

Dispensing Accuracy & Precision NOT tested by sealed source checks – need to test end point product

Geometrical Checks (Tested to EC61145) Fixed geometry design

Temporal/Power Cycle Stability Repeat testing

Need specific RN (adjusting gain of separate current ranges?) & at least 3.7Mq, with source assay uncertainty <3%

Cs-137 - we had & just about hot enough

Co-57 – only had a penpoint marker source, made temp jig to hold it in position, low activ so gave warning message - but worked !

Important to have accurate reference activity for each source - we remeasured sources

User adjusts gain for each source until difference in measured:expected minimised (<3% to pass)

Sealed Source Calibration

Before first use then quarterly recommended

User instructions -> 1GBq vial in QC dipper (1.7GBq actually used)

Enter pre-measured vial activity & leave overnight (15h to decay to 3.7MBq)

Automatic program logs data & displays results, relative to reference activity

Results graph displayed & retained in system memory, summary printed

Graph ?exportable via USB or wi-fi

Intego linearity -0.1% to +0.6% Atomlab -0.1 to +0.2% (both wrt 970MBq point)

Intego result quoted wrt first point 0.0 to +0.8%

Linearity

Zero check

Background check

Bias current adjustment

Constancy Check – your choice of sealed source Accuracy : 1-10% Constancy : 1- 5% (Definition unclear)

Battery / Voltage Check

-5

-4

-3

-2

-1

0

1

2

3

4

5

1 2 3 4 5 6 7 8 9 10 11 12

% D

evia

tio

n fro

m R

efe

ren

ce

Session No

Intego Cs137 Accuracy Deviation (0-10% accepted range)

Talbot, JNM 2009

Dispensed vs presc so relative precision

100 Intego infusions of 555MBq

87 within <1% of presc, 1 over 5%, range -4.7 to +9%

Lecchi, EJNMMI 2012

Intego activity vs external (PET Dose) calibrator

No geom/vol corr ?

12 lots consecutively dispensed

162-405 MBq

-3.1 to +2.7% diff

EANM guidelines ±3%

Observed dose accuracy using

Medrad Intego PET Infusion

System, Talbot et al JNM 2009;

50 (Supp 2):2030

End-Point Tests

Validation of new protocol for FDG infusion

using an automated combined dispenser and

injector, Lecchi et al EJNMMI 2012; 39:1720-

29

Intego activ vs Atomlab 500 calibrator

30-40ml dispensed into bottle (need large bore shield)

Subdispense by weight (calib scales) into known geometry & volume (5ml syringe)

Apply F18 syringe corr & decay correct all data to derive dispensed bottle activity

Range of activities & concentration

Consecutive tests and repeat tests separated by days/month

Leeds End-Point Tests

11 dispensing tests in 4 sessions over 7 weeks, 4th Sept – 23rd Oct 2012

6 tests in 3 sessions before 1st patient use

Used shield for liquid I131 tx (large bore)

Limited by time, available F18 & large dilution factor (difficult to re-use F18 given fixed constraints on total activ & concentration)

Plastic bottle & 40ml vol response estim 0.94-0.96, needs defining accurately wrt vial standard

Intego

Daily variation Cs137 6.19 ± 0.02MBq

Precision ? Can’t rpt same aliquot

Non-lin ±0.6%

Accuracy wrt sealed source calib 0.1% ?

Accuracy wrt F18 =?

Atomlab

Daily varn F18 Mean/ SD 4.98 ± 0.01MBq

Precision of rpt measurement < 1%

Non-lin ±0.2%

Accuracy wrt 20 std – corrected, prec<1%

20 std accuracy wrt F18 standard =?

Redispensing to std geom < 1%

Uncertainties

Intego 100 Vs Atomlab 500 F18 Measurements

0

100

200

300

400

500

600

700

1 2 3 4 5 6 7 8 9 10 11

Dispensing Session

Dis

pe

ns

ed

Ac

tiv

ity

MB

q

Atomlab

Intego

Intego 100 Vs Atomlab 500

F18 Measurements

0

100

200

300

400

500

600

700

0 100 200 300 400 500 600 700

Atomlab Activity (MBq)

Inte

go

Ac

tiv

ity

(M

Bq

)

Intego / Atomlab Ratio

0.60

0.70

0.80

0.90

1.00

1.10

0 1 2 3 4 5 6 7 8 9 10 11 12Measurement Session

Inte

go

: A

tom

lab

Ra

tio

Intego : Atomlab ratio 0.95 to 1 (estim unc <3%) for 11 disp on 4 days over 7 weeks

Good agreement & repeat checks for similar activities consistent over time

Geom bottle corr needed if measuring directly (preferable as max meas activ & cuts dose)

Ongoing tests would assess long term stability

Which machine is closer to ‘true’ ? …

Other systems will have diff ‘features’ to workaround for testing e.g. bespoke dose cartridges need new geom corrections

2008 NIST study : 39 calibrators & traceable calibrated Ge68 source.

Found systematic differences between calib types for F18 of 6-10%, average 7%, consistent across sites

RadQual’s own audit of 100 machines shows some models even exceed 15%

Medrad may modify systems to use Ga68 accuracy source in future

Would help improve accuracy in meas of patient activ but also with QA of PET scanners & PET-based quantification, where these use F18 sources measured on-site

Ge-68 Calibrated

Reference Source

•T1/2 270.95 days

•Source calibrated against

NIST standard (for Ge68 &

F18 equivalent activity)

Belgian Nuclear Research Centre (SCK•CEN), Optimization of Radiation Protection of Medical Staff (ORAMED) http://www.oramed-fp7.eu/en/Presentations.

Extremity doses of nuclear medicine personnel: a concern Kemerink, Vanhavere, Barth & Mottaghy Eur J Nucl Med Mol Imaging. 2012 March; 39(3): 529–532. B.

E. Zimmerman, et al (2001),“Radioassays and experimental evaluation of dose calibrator settings for 18F”, Appl. Radiat. Isot., 54: 113-122.

J. T. Cessna, et al.(2008), “Radionuclide calibrator measurements of 18F in a 3 ml plastic syringe”, Appl. Radiat. Isot., 66: 988-983.

Observed dose accuracy using Medrad Intego PET Infusion System, Talbot, Mountz & Coates J Nucl Med. 2009; 50 (Supplement 2):2030

Validation of a new protocol for (18)F-FDG infusion using an automatic combined dispenser and injector system. Lecchi et al. Eur J Nucl Med Mol Imaging. 2012 Nov;39(11):1720-9.

Garry MacDermott (Medical Physics)

Anne Richardson (Radiopharmacy)

Fiona Ware (Nuclear Medicine)

Keith Alberg (RadQual)

Thanks for listening & thanks also to these people