From October 2017 to May 2018, 212 patients were examined with 18F-PSMA-1007 PET/CT as part of clinical routine. Of these patients, 100 were referred for the detection of recurrent PCa. The patients received primary therapy for PCa a median of 44.3 months before PSMA imaging (range 2–314 months). In seven patients, the exact time of the first therapy for PCa was not available. Some of the patients had undergone CT, MRI or bone scan before PSMA imaging. However, a systematic comparison of these data was not possible since the intervals were highly variable and different procedures had been performed. All other imaging studies performed before PET/CT had been negative. Of the 100 patients, 28 had been analysed previously in a dual time scanning analysis .
Patient characteristics are given in Table 1. Patients with no primary therapy with curative intent or patients referred for PSMA radioligand therapy were not included in the current analysis (Fig. 1). Prostatectomy, radiation beam therapy and androgen-deprivation therapy had been performed in 92%, 45% and 27% of the patients. Radiation beam therapy in addition to surgery had been performed in 38 patients (38%) and 10 patients (10%) had received all three therapy modalities. All patients received detailed information about the imaging procedures and provided signed informed consent according institutional guidelines.
Imaging procedures and preparation of 18F-PSMA-1007
18F-PSMA-1007 was produced in a GE TracerLab MX synthesizer according to the one-step procedure described by Cardinale et al. and standard operation procedures described previously [14, 15] including sterile filtration of the final batch solution. 18F-PSMA-1007 precursor, cassettes and reagents for the synthesis of 18F-PSMA-1007 as well as the synthesis sequence for fully automatic production with a GE TracerLab MX module were obtained from ABX GmbH (Radeberg, Germany). The final injection solution of the 18F-PSMA-1007 batch was clear, colourless and particle-free, and had a mean radiochemical purity of 96.5 ± 1.1% (range 95–99%) as determined by high-performance liquid chromatography. Unreacted 18F-fluoride or 18F-fluoride resulting from compound cleavage was not detected by thin-layer chromatography. The pH of the batch solution ranged from 5.9 to 7.8 and the endotoxin content was <5.0 endotoxin units/ml. The concentrations of ethanol and dimethyl sulfoxide (DMSO) as residual solvents were measured by gas chromatography (ethanol 29.6–31.6 mg/ml; DMSO 0.25–0.68 mg/ml). The osmolality ranged from 1,110 to 1,300 mOsmol/kg.
Patients received 4 MBq/kg body weight with a maximum of 400 MBq per patient (mean injected activity 338 ± 44.31 MBq). Scanning was performed 120 min after injection from the lower limbs to the skull. Patients were asked to empty their bladder before the scan. Images were acquired with a scan time of 3 min per bed position on a Siemens mCT scanner (Siemens Healthcare, Knoxville, TN). Images were reconstructed using the standard software provided by the manufacturer. For attenuation correction, a low-dose CT scan was performed in accordance with the PET imaging. Contrast-enhanced CT of the abdomen and pelvis was only performed if no recent CT or MRI scans were available.
Coregistered images were analysed using syngovia software, version: VB20A (Siemens Healthcare). According to institutional procedures all scans were analysed by two board-certified nuclear medicine physicians and radiologists at an interdisciplinary conference for reporting. Absence of morphological changes was regularly found and were classified as bone metastases and local recurrence. The sensitivity of CT for these types of metastases is known to be limited, and thus high focal tracer uptake in these areas was considered suggestive of bone metastases or local recurrence despite a lack of morphological correlation. In lesions characteristic of PCa, volumes of interest were placed on the plane with highest uptake, and maximum standardized uptake values (SUVmax) were measured and documented. Focal tracer uptake above local background in morphologically visible lesions on CT was considered as PSMA-positive. Any visible PCa lesions were analysed unless the patients had more than three lesions, in which case, a maximum of three lesions were analysed. This kind of selection avoids overestimation of SUVs as otherwise dominant lesions would be preferentially selected. Typical pitfalls such as PSMA uptake in sacral and coeliac ganglia or in the stellate ganglia were frequently observed but were not considered pathological .
SPSS Statistics 25 (IBM Inc. Armonk, NY, USA) was used for statistical analysis. Descriptive statistics are absolute and relative frequencies, mean or median and standard deviation or range, were used to characterize the study population. For subgroup analysis, patients were divided into four groups depending on their prostate-specific antigen (PSA) level: ≤0.5, 0.51–1.0, 1.1–2.0 and >2.0 ng/ml. The Mann-Whitney test was used to evaluate the significant differences of the median SUVmax (of the lesion with maximum uptake from each patient) between PSA groups. A P value <0.05 was considered significant and noticeable.