Patients
Nineteen therapy-naïve, oligo-metastasized, biopsy proven prostate cancer patients with a median age of 73 years (range: 57-80 years) who were foreseen for local ablative radiotherapy underwent 68Ga-PSMA-11-PET for primary staging before start of androgen deprivation therapy (median: 14, range 0-59 days). All patients were discussed in an interdisciplinary tumor board. After six months a local ablative radiotherapy to all known lesions was planned, and a re-staging PET was performed (median: 156, range: 61-289 days after start of ADT). The two time points were labeled as T1 and T2, respectively. The data were obtained between 11/2016 and 01/2020 and were retrospectively analyzed.
Written informed consent was obtained from all patients for the clinically indicated examination and the consecutive scientific analysis of their clinical and imaging data. The institutional review board of the local ethics committee at our medical faculty approved this analysis.
Radiotracer preparation
The radiotracer 68Ga-PSMA-11 was synthesized as in clinical routine and as previously described (25).
Imaging protocol
No specific patient preparations were required for 68Ga-PSMA-PET.
For the 19 examinations at T1 a median of 153 MBq (range: 90-206 MBq) was applied and acquisition started with a median of 115 min p.i. (range: 89-168 min), while for the examinations at T2 a nearly equal median of 155 MBq (range: 62-190 MBq) was applied and imaging started with a median of 116 min p.i. (range: 92-140 min).
The 38 examinations were performed on either PET/MRI or PET/CT 1 or PET/CT 2. Ten out of the 19 patients underwent both examinations on the same device.
The PET/CT scans until 08/2019 (PET/CT1) were acquired with a Biograph 16 (Siemens CTI, Knoxville, Tennessee, USA). Eight to 9 bed positions were obtained with 3 min scan time each. The PET/CT scans after 08/2019 (PET/CT2) were acquired with a Biograph Vision 600 (Siemens Healthineers, Knoxville, USA). The emission PET scan was obtained using continuous bed motion with a speed of 2.9 mm/s being equivalent to 1.5 min per bed position.
The PET/MRI scans were acquired with a 3 Tesla Ingenuity TOF PET/MR (Philips Medical Systems, Best, Netherlands). Ten bed positions were acquired with a scan time of 3 min each.
Imaging reconstruction
The CT 1 images were reconstructed using an ordered-subset expectation maximization (OSEM) algorithm with 6 iterations and 4 subsets with a 168x168 matrix. Plain CT scans for attenuation correction were performed in a craniocaudal direction from the skull base to the upper thighs. Scanning parameters included 100 mAs, 120 kV, online tube current modulation, 1.5 mm slice collimation, 0.5–0.75 s rotation time, and reconstruction of 5 mm slices.
The CT 2 images were reconstructed using the TRueX algorithm with 4 iterations, 5 subsets, Time-of-flight (TOF) application and without filtering. The resulting PET images had an image matrix size of 440x440 with a voxel size of 1.65 x 1.65 x 3.0 mm. A standard low dose CT was acquired from the whole body (X‐ray tube current of 10 mAs, tube voltage of 100 kV, spiral pitch factor of 1.5, 3.0 mm slice thickness) and used for scatter correction of the subsequent PET scan.
Image analysis
A Nuclear Medicine physician (SH) and a Radiologist (RW) both experienced in PSMA-PET reporting used Syngo.via Software (VB30a, Siemens Healthineers, Erlangen, Germany) to determine pathologic uptakes and to identify the reference lesions. Senior Consultants in Nuclear Medicine (KZö) and Radiology (DF) retrospectively confirmed the findings of both of them.
At first, all scans were evaluated visually. Pathologic uptakes were initially assumed if a lesion shows a tracer uptake higher than the local background (26). Depending on the localization, they were rated as local (prostate) tumor, lymphonodal or bone metastasis. For subsequent quantitative analysis, volumes of interest (VOI) sufficiently large for covering the whole lesion were inserted over each pathologic lesion and SUVmax as well as SUVmean of each lesion were acquired. The resulting volumetric parameters were the PSMA-derived tumor volume (PSMA-TV) based on a 45% cut-off of the SUVmax, as suggested by Schmuck et al. (23), and the total lesion PSMA (TL-PSMA), which is a product of PSMA-TV and the SUVmean of that lesion. The concept of these metabolic volumes is adapted from FDG imaging and PSMA-TV calculation is equivalent to the metabolic tumor volume (MTV) while TL-PSMA is calculated equally to the total lesion glycolysis (TLG) (28).
Sufficiently large (27) VOIs were further inserted in reference regions: liver (3 cm diameter), the thoracic aorta (2 cm diameter) and the parotid glands (1.5 cm diameter), and the SUVmax and SUVmean values were calculated. For the parotid glands the values were averaged.
In order to make the uptake values more comparable between the different devices and different reconstruction algorithms ratios to the respective liver SUVmean were calculated (LQ) for SUVmax, SUVmean and TL-PSMA and compared.
For the same reason, each lesion was scored according to the miPSMA expression score (27). The score ranges from 0 (uptake < blood pool) to 3 (uptake ≥ parotid gland). It was determined based on the SUVmean of both the lesions and the reference lesions. If a lesion was not separable from the local background in one time point it was scored as 0, regardless of its SUVmean. To evaluate the patients total tumor burden the sum of the score of all lesions was calculated as well.
Furthermore, each patient was staged using the miTNM expression score. Since there was no contrast enhanced CT or MRI simultaneously acquired after ADT, there was no T Stage to be compared.
Statistical analysis
To compare different PSMA parameters lesion-based characteristics and the PSA value between the two time points T1 and T2, the paired Wilcoxon signed-rank test was applied. For the comparison of parameters between independent patient groups or lesions, the Mann-Whitney-U test was used. Correlations between PSMA parameters, lesion-based characteristics and PSA values were evaluated by the Spearman correlation coefficient r. All statistical analyses were performed using SPSS 25 (IBM Corporation, Armonk, NY, USA). Two-sided tests were performed and p-values below 0.05 were considered as statistically significant.