“The fall and rise of sub 10MeV cyclotrons for PET” John C Clark (College of Medicine and Veterinary Medicine, Univ. Edinburgh, UK) Scanditronix Users Meeting University of Birmingham UK 1-3 September 2014

2006 IAEA

Allis Chalmers 6.5 MeV deuteron only cyclotron at The Mallinckrodt Institute of Radiology Washington University St Louis Massachusetts General Hospital had the second machine.1960’s period

Mainly used for oxygen-15, carbon-11 and fluorine-18

First oxygen-15 target for clinical uses

Allis Chalmers cyclotron at Washingthon University St Louis 6Mev deuterons

In the late 70’s and early 80’s several groups looked at the cross sections for the production of the main PET radionuclides 11C,18F,15O and 13N and came to the conclusion that an on site* 8 MeV proton cyclotron of adequate intensity could with the use of highly enriched stable isotope targets meet all the demands of clinical PET scanner clinics

14N(p,a)11C or 11B(p,n)11C 18O(p,n)18F 15N(p,n)15O 13C(p,n)13N

*Note: This was long before distribution of 18F products esp FDG was established.

18O(p,n)18F Reaction

The most convenient

chemical form of the target

material is in the form of

oxygen-18 enriched water.

This is the reaction that is

used by nearly all facilities

for the production of 18FDG

The nuclear reaction cross

section is shown on the

right and it should be noted

that the peak of the

reaction is about 6 MeV

and it tails off rapidly above

11 MeV.

Carbon-11 Production

• Three potential nuclear reactions

– 14N(p,α)11C

– 11B(p,n)11C

– 12C(p,pn)11C

Production Routes

0.0

50.0

100.0

150.0

200.0

250.0

300.0

350.0

400.0

450.0

500.0

0 5 10 15 20 25 30 35

Energy (MeV)

Cro

ss s

ecti

on

(m

b)

11B(p,n)11C

14N(p,a)11C

12C(p,pn)11C

The cross sections for these three reactions are given in the table below

In terms of the yield

of the nuclear

reactions, it is clear

that the best choice

is the 11B(p,n)11C

reaction

Machine builtin New Zealand for Knoxville company but never worked due probably due to centre region design issues. Commercial pressures in Knoxville terminated the project. Alleged to relate to competition with the RDS112 project at the time!

ORBIT 8 MeV proton positive ion sector focussed cyclotron concept (1982)

Japan Steel Works BC168 16Mev proton 8Mev deuteron positive ion cyclotron

Other similar performance positive ion machines of the same era Scanditronix MC-16 Cyclotron Corporation CS-15 CGR 325 AEG

CGR MeV 325 cyclotron

Karloinska MC 16 now in Lund twin of John’s Hopkins machine now in Seattle en route Alaska

OXFORD INSTRUMENTS “OSCAR” 12MeV proton Superconducting Cyclotron

Oxford Instruments Oscar in Madrid still in operation now with an IBA Cyclone 18/9 for company.

CTI RDS-112 11MeV protons 4 targets

The RDS-111 followed and could accommodate up to 8 targets in a carousel format but was superseded by the Eclipse which has 2 sets of 4 targets to enable better cooling at higher beam currents available with the Eclipse and also self sheilded.

Tandem Cascade Accelerator at Washington University St Louis approx 4MeV deuterons

Prototype IBA Cyclone 3D 3.5 MeV deuterons “Oxygen-15 Generator”

At The Medical Research Council Cyclotron Unit at Hammersmith Hospital

IBA Cyclone 3D decommissioning incident at Hammersmith Imanet 2011

Prototype Petrace 200 now GE PT800 resited and refurbished I Aarhus DK

IBA Cyclone 10/5 self shield opened. Targets are distributed around the vacuum chamber inside the magnet yolk

Self shielded Cyclone IBA 10/5 now upgraded to 11MeV protons and 5.5MeV deuterons

Summitomo

HM-12 12MeV protons 6MeV deuterons evolved from licenced GE Minitrace

HM-7 Vertical, self shielded (based on Minitrace concept) 2.8 x1.6 x 2 h (m) 7.5 MeV proton 70 µA 3 exits ports / 1 extraction 18F : 1 Ci, 60 min, 70 µA § Room 6x 3.6 m / height 2.7 m Weight 30 Tons (shield inc.)

Technical Specifications 7.5 MeV Positive Ion Cyclotron

Internal targets

F-18, C-11 in development

1.16 T Magnet

<5 mA Beam current

<300 uL Target Volume

Compact Accelerator

9.15

16.9

22.15

33.8 36.1

49.6

0

10

20

30

40

50

60

10 20 30 40 50 60

mCi F-18 Production

Average Yield Curve for 250 Bombardments on two different accelerators with 3.5 uAmps

target current +/- 10%

Bombardment Time

Simple Accelerator Consumables ease Maintenance

Internal target

• Small volume <300 microliters

• Simple rebuild, replacement

Replaceable Internal Ion Source

• Detachable anode

• Simple swap limiting maintenance

• No expertise required

Self shield open view of ABT cyclotron in Newcastle UK

ABT Chemistry Process and QC module

GE Prototype 8 MeV proton PT-600 cyclotron

Target positions x 3

Turbo pump

Mikael Jensen with new “toy” at RISO

Tim Antaya Ionetix USA

Prototype Superconducting 12MeV proton cyclotron magnet.

CIEMAT Madrid/CERN consortium

AMIT Superconducting 8.5 MeV proton H- external targets

Summary Several projects are underway to attempt to bring very small cyclotrons to the point where they are able to provide “unit” doses on demand. The footprint when shielded is likely to be less than currently available 11 to 19 Mev Machines. But it is still unclear that the running costs will be affordable with the large overhead cost of disposables and QC functions for a single dose production. Pharmaceutical Regulatory issues are likely to be an on-going concern. Will cryocooled superconducting machines make an impact in this field? Maybe yes based on size, weight and running costs but they will still suffer the same chemistry production issues as standard resistive machines