Routine production of 18F‾ with a beam current of 200 µA on a GE PETtrace cyclotron: Experience over > 18 Months

Introduction The increasing demand for [18F]FDG for clinical PET-CT and the efficiencies associated with large production runs have encouraged endeavors to increase the amount of 18F− produced by cyclotrons in a single run. The amount of 18F− is determined by the saturation yield of the nuclear reaction, the irradiation time and the beam current striking the target. The saturation yield is a function of beam energy (typically fixed for PET cyclotrons), the enrichment of the H218O (typically > 97 %) and the efficiency of the target design. Target design has already been optimized on current systems. Diminishing gains in activity are achieved by extending the irradiation time much beyond 3 hrs, so the main focus has been to increase beam current onto the targets. Increasing the beam current requires: i) a cyclotron capable of producing the increased beam current; ii) targets that tolerate the beam current without appreciable loss in saturation yield; iii) sufficient shielding of the cyclotron and hot cells to accommodate the proportionally larger radiation dose rates during higher current irradiation and from the larger activities delivered to the hot cells. We reported [1] that the self-shielded targets fitted to our cyclotron can accommodate 100 µA currents without appreciable loss in saturation yield. We also identified the potential of routine production at 200 A (100 A per target in dual target irradiation mode), but had not establish its long-term viability in routine use. We present our experience in using 200 µA for routine production of 18F- since September 2012. Material and Methods Our PETtrace cyclotron was installed in 2002 and has been used for routine production of various 18F and 11C tracers since January 2003. It has been upgraded incrementally so that it is now equivalent to a current generation PETtrace 880 cyclotron, which is specified at a total beam current of 130 µA. The only components on our cyclotron currently not part of the standard PETtrace 880 cyclotron configuration are the self-shielded targets and a license which allows total target beam current of 200 µA. The self-shielded targets utilize a W/Cu alloy for the main body of the target surrounding the Havar foil to provide shielding from the Havar foil by a factor of about 10 and shielding of any remnant 18F- activity in the targets by a factor of about 100 [1]. The niobium target chamber is the same size as used in the standard GE Nb25 targets. However, it dispenses with the He cooling and the vacuum foil. Only the water foil is used, which is directly exposed to the vacuum in the chamber. Foil cooling is through the water in the target chamber. One of the issues that we previously identified [1] is beam stripping by gas molecules in the vacuum tank. The amount of beam that is stripped and which impacts on components in the cyclotron is proportional to the beam current. At high currents, this can result in a runaway condition, where the effects of the stripped beam deteriorate vacuum; this then results in more beam stripping and more severe effects. The effect of diffusion pump maintenance on vacuum system performance and on the reduction of beam stripping was investigated as part of this study. We have previously found that running the ion source gas at a low flow rate (2 sccm) when cyclotron is not used greatly reduces deterioration of ion source performance over time and with use [1]. This gas flow also appears to have a beneficial effect on the vacuum. Ion source gas flow when cyclotron is off has been employed throughout the evaluation period. [18F]FDG was produced with TRACERlab MXFDG modules or FASTlab modules using both Phosphate and Citrate cassettes. Stability studies of [18F]FDG were performed to ensure it met specifications over the specified expiry time. Our current stabilization regime did not have to be adjusted for the higher activities produced with the higher beam currents. [18F]FDG yields were calculated using input activity estimates from saturation yield and beam time and current and the non-decay corrected [18F]FDG activity measured at the end of synthesis. Thus yield calculations include target yield variations and losses in the transfer lines and not just synthesis yield. Results and Conclusion The flip-in probe to extraction foil transmissions as a function of ion source gas flow are given in TABLE 1. Transmission decreases with increasing ion source gas flow, as expected for a system with an internal ion source. In addition, diffusion pump maintenance had a positive impact on the transmission and this is of particular benefit at the higher beam currents where minimising beam stripping becomes more critical. The ion source output, however, decreases with decreasing ion source gas flow; hence ion source gas flow is a compromise between ion source output and probe to foil transmission. We currently use a gas flow of 5.5 sccm for our 200 µA runs. Over the period from 1st September 2012 to end of March 2014, a total of 419 [18F]FDG produc-tions were performed at total target beam currents ranging from 160 µA to 200 µA, with 227 production runs being performed at 200 µA. Beam times were typically 90 to 120 min, with some productions up to 180 min. The [18F]FDG yields are summarized in TABLE 2. The yields for the FASTlab phosphate and citrate cassettes have been listed separately in TABLE 2 as they are known to be different [2,3]. The yields obtained with the TRACERlab MXFDG are also shown. The yields at 200 µA total target current are not appreciably different from those at 120 µAh, respectively. As more experience has been gained with the self-shielded targets, service interval is actually being extended from about 10,000 µAh to 20,000 µAh, despite the higher beam currents. Diffusion pump maintenance is currently recommended every 5 years, but a 2 year maintenance interval may be advantageous for 200 µA, given the observed deterioration over a 5 year period and the improvement in performance post service (Table 1). The more frequent service is associated with the additional costs of diffusion pump oil and an extra day of scheduled down-time. Typically, vacuum is sufficiently well established 24 h after opening of the vacuum tank to run 200 µA beams with the vacuum and beam conditioning that we employ. The targets generally have coped well with the 100 µA per target current (200 µA total beam current for dual target irradiation) over this 18 month period. However, currents of 80 µA to µ100 A per target in dual target irradiation mode reduce the tolerance to sudden increases in one of the target currents. There were 4 occasions (2 test beams and 2 production beams) when there were sudden increases of target current from 90 µA and 100 µA to about 150 µA. The rapid increase in heat deposited on the foil and target chamber and the resultant rapid pressure rise in the target chamber could not be withstood by the foil and target foil rupture ensued. This compared to 1 target foil issue over a similar period of time (18 months) at lower beam currents on the standard Nb25 target. Three separate causes were identified for these overshoots in target current: 1) behavior of control system when beam is allowed to continue past the set time; 2) large changes of set current of one of the two targets irradiated during a dual irradiation test beam and 3) an issue with DEE voltage regulation caused by the mechanical flap controls. These issues have been addressed by procedural changes (issues 1 and 2) and by fitting an available upgrade of the mechanical flap control mechanism (issue 3). The two target foil ruptures during production did not cause cancellation or delays to patient scanning, as the demand could be met by multi-ple productions and deliveries from the unaf-fected target. No unscheduled down-days occurred during the evaluation period. We have been able to achieve routine operation at 200 µA beam current through careful optimization of the critical components and parameters and a maintenance regime that we have detailed previously [1]. This maintenance scheme has not changed for the routine 200 µA operation. The safety margin, however, is reduced and so careful monitoring of the system is required to ensure that issues in one of the subsystems do not cause major events such as target foil ruptures. Our [18F]FDG yields have been maintained at the higher current and 200 µA allows large quantities of [18F]FDG to be produced routinely in a single run with relatively short beam times