68Ga-PSMA PET/CT guideline page 1
68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for
prostate cancer imaging: version 1.0
SUPPLEMENTAL MATERIAL
Quality control and inter-institution PET/CT system performance harmonisation
PET/CT system quality control
Clinical interpretation of 68Ga-PSMA PET/CT is based on visual analysis. Semi-quantitative
SUV (SUVmax) can be measured and documented for key lesions. Reproducibility and image quality are of critical importance especially for communication between different centers. A consistent and rigorous PET/CT scanner quality control program can contribute to minimization of measurement errors and help maintain image quality associated with
PET/CT scanner equipment.
There are three PET/CT QC program categories for 68Ga-PSMA imaging, which are identical to those employed with 18F-FDG tumor imaging. These categories, as previously described in the EANM Procedure guidelines for 18F-FDG tumor imaging, [1] are:
Daily QC & Calibration of both the PET and CT components of the imaging system
Calibration QC and cross-calibration of the PET/CT system with a dose calibrator
which is used to measure the patient-specific 68Ga-PSMA administered dose
Image quality and recovery coefficients (IQRC)
The QC measures detailed below are meant to assure, to the extent achievable, direct comparability of imaging data (SUV and absolute activity concentration) between sites with a minimum of variance and bias. These measures are potentially in addition to any QC requirements dictated by national law or legislation or those recommended by local nuclear medicine societies. 68Ga-PSMA PET/CT guideline page 2
Daily QC
The Daily QC requirements for 68Ga-PSMA studies are identical to those previously described in the EANM Procedure guidelines for 18F-FDG tumor imaging and are repeated here, with minor modification, for completeness. The aim of daily QC is to determine whether the PET/CT system is functioning in accordance with manufacturer’s specifications, and specifically to check for detector failure and/or electronic drift that might impact quantitation and image quality. All modern commercial PET/CT systems are equipped with automated or semi-automated procedures for performing daily QC. For some systems, the daily QC includes tuning of hardware and/or settings (such as gains). In all cases all daily QC measures and/or daily set-up/tuning measurements should be performed according to the manufacturer’s specifications. Users should both check and document whether the daily QC meets the specifications. When available, a daily PET/CT study of a cylindrical phantom filled with 68Ge or another long-lived positron-emitting isotope should be acquired [2]. This test enables assessment and reduction of longitudinal variability due to calibration error and/or
PET/CT system sensitivity drifts. Inspection of uniformity and quantitative accuracy of the reconstructed PET image may help identify technical failures that were not detected using the routine daily QC procedures. In addition sinogram data should be inspected to check for detector failure.
Calibration QC and cross-calibration of PET/CT systems
The aim of cross-calibration is to determine the correct and direct cross-calibration of the
PET/CT system with the institution’s own dose calibrator which is used to determine patient- specific 68Ga-PSMA activities [3]. Most PET/CT sites cross-calibrate their PET/CT scanners with their dose calibrators using 18F. Procedures to perform this calibration are generally provided by the PET/CT manufacturer and are also described in the UPICT oncology 18F-
FDG PET/CT protocol [4] and by EANM Research Ltd (EARL) [5]. This is not sufficient to assure quantitatively accurate 68Ga imaging because 68Ga has a different positron branching ratio and an additional prompt gamma (1077 keV, 3.2%), which will impact both the 68Ga-PSMA PET/CT guideline page 3 calibration of the dose calibrator and the PET scanner.
There are two general methods for cross-calibrating the PET/CT scanner to the dose calibrator for 68Ga. In the first method the 18F cross-calibration is used as the reference standard, followed by an additional step whereby a known quantity of 68Ga measured in the site’s dose calibrator is injected into an aqueous 20 cm diameter cylindrical calibration phantom of known volume and imaged on the PET/CT system. The imaged-based PET/CT measured 68Ga concentration (MBq/mL) is then compared to the known concentration. The difference in these concentrations can be corrected by exactly adjusting the 68Ga dose calibrator gain setting to compensate for the measured percent differences. This method will be critically affected by the presence of absence of prompt gamma correction within image correction algorithm.
In the second method, a commercially available long-lived 68Ge/68Ga dose calibrator source that is pre-calibrated to an internationally recognized (NIST) standard can be used to directly calibrate the dose calibrator to this standard 511 keV source. The PET/CT scanner is then cross-calibrated directly to 68Ga (not 18F) using methods similar to those described in [4-5], but with 68Ga and not 18F. Subsequent to the 68Ga-based cross-calibration, it is recommended that the site checks that the 18F cross-calibration is still accurate. If it is not, the 18F gain setting on the dose calibrator must be adjusted to compensate for any measured bias. The second 68Ge/68Ga based method is preferred, as all measurements are based upon an internationally recognized (NIST) reference source. However, it requires that the site invest in the NIST traceable dose calibrator source. In both methods it is recommended that the cross-calibration for 18F and 68Ga is confirmed with additional phantom scans to assure that any adjustments to the measurement systems were correct. Centres should be cautioned to not base their cross-calibration on stated measurements on 68Ge/68Ga cylindrical 20 cm diameter epoxy phantoms. Although convenient, and the stated activity and volume may be accurate, the attenuation properties of the epoxy do not match with PET/CT attenuation 68Ga-PSMA PET/CT guideline page 4 lookup tables and can result in large (>5%) biases.
Image quality and recovery coefficient harmonization
Differences in both SUV quantification and lesion detectability between centres are inevitable because of inherent differences between PET/CT scanner models and reconstruction and data analysis methodology [6-7]. To this end an IQRC QC procedure has been developed:
To determine/check the correctness of a calibration and quantification using a non-
cylindrical (calibration) phantom containing a set of high-contrast spherical objects.
To measure standardised activity concentration or SUV recovery coefficients as a
function of sphere (tumor) size.
The main aim of the IQRC QC procedure is to guarantee comparable quantitative PET/CT system performance with respect to SUV recovery and quantification. Details on the IQRC
QC procedure, SOP and standardised specifications are provided by EARL [5]. The EARL methodology has not yet been exhaustively tested using 68Ga, but under standard phantom imaging conditions it is anticipated that current specifications will hold.
Limitations
68Ga-PSMA is a relatively new clinical tracer that has several properties that challenge and to some extent limit the full applicability of the above-described QC procedures to achieve their goals. First, the 68Ga 1077 keV prompt gamma, although scanned, has been demonstrated to have an impact upon currently available scatter corrections, particularly in very high contrast situations. This may impact measurement and detectability of lesions near high contrast objects like the bladder. Second, the very high target to background properties of 68Ga-PSMA commonly results in SUVs substantially higher than those typically encountered in 18F-FDG imaging and those simulated by the EARL phantom methodology. As these high SUV situations are not tested in the EARL phantom procedure, the full-applicability of the IQRC specifications are assumed, but not yet fully tested. A multicentric SNMMI initiative is currently undertaken to validate IQRC specifications. 68Ga-PSMA PET/CT guideline page 5
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