Detection Rate of 18F-Choline PET/CT and 68Ga-PSMA-HBED-CC PET/CT for Prostate Cancer Lymph Node Metastases with Direct Link from PET to Histopathology: Dependence on the Size of Tumor Deposits in Lymph Nodes.

Accurate detection of prostate cancer lymph node metastases (LNM) through PET/CT before lymphadenectomy is crucial for successful therapy. PET/CT with choline derivatives used to be the standard tool for imaging metastases, whereas 68Ga-PSMA (prostate-specific membrane antigen) PET/CT was introduced recently. Both PET techniques were investigated with respect to what extent the detection rate of LNM depends on the size of tumor deposits (TDs) within LNM. Methods: Documenting the switch from the use of 18F-choline to 68Ga-PSMA in 2014, we used 2 patient cohorts undergoing a template lymphadenectomy because of a PET/CT indicating LNM. Forty-four and 40 patients underwent PET/CT with 18F-choline or 68Ga-PSMA ligand, respectively. In total, 226 LNM (125 18F-choline, 101 68Ga-PSMA) originated from 73 salvage lymphadenectomies at biochemical recurrence and from 11 primary lymphadenectomies at radical prostatectomy. LNM eligible for direct correlation of PET/CT to histopathology were identified from lymphadenectomies conducted in small anatomic subregions, with 1 LNM (condition 1) or 1-2 LNM (condition 2). Longitudinal and short diameters of TD within LNM were determined by histopathology, allowing linking of the size of TD in LNM to the detection threshold of PET/CT. Diameters associated with a detection rate of 50% and 90% (d50%, d90%) were calculated on the basis of logistic growth curve models fitted. Results: Gleason score, number of removed LNs, and subregions for lymphadenectomy per patient did not differ significantly between the 18F-choline and 68Ga-PSMA groups. The median prostate-specific antigen level at imaging and number of LNM per patient were significantly higher in the 18F-choline group (3.4 ng/mL, n = 34) than in the 68Ga-PSMA group (2.2 ng/mL, n = 28; both P < 0.05). Longitudinal and short diameters of TD in LNM to reach d90% were 11.2 and 7.4 mm, respectively, for 18F-choline PET/CT and 6.3 and 4.9 mm, respectively, for 68Ga-PSMA PET/CT. Corresponding diameters to reach d50% were 5.5 and 3.3 mm, respectively, for 18F-choline PET/CT and 3.7 and 2.3 mm, respectively, for 68Ga-PSMA PET/CT. Detection rates were significantly higher under 68Ga-PSMA (P = 0.005 and 0.04 for longitudinal and short diameter). Conclusion: 68Ga-PSMA PET/CT is superior to 18F-choline PET/CT in the detection of LNM. Whether those results will lead to an improved patient outcome after 68Ga-PSMA PET-guided therapy needs to be investigated by further studies.

68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging.

The study aims to investigate the presence of physiologic prostate-specific membrane antigen (68Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Methods: Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled with 68Ga-gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid (68Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of 68Ga-PSMA PET-positive cervical, celiac, and sacral ganglia was determined, and the configuration and SUVmax of each ganglion were measured. In addition, the configuration and SUVmax of adjacent lymph node metastases in the respective region (cervical, celiac, or sacral) were determined. Results:68Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral ganglia, in 369 (92%) patients in cervical ganglia, in 363 (89%) patients in celiac ganglia, and in 183 (46%) patients in sacral ganglia. The 68Ga-PSMA-ligand uptake was highest in celiac (mean SUVmax, 2.9 ± 0.8 vs. cervical mean SUVmax, 2.4 ± 0.6) and sacral (mean SUVmax 1.7 ± 0.5; both P < 0.0001) ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the 68Ga-PSMA-ligand uptake in cervical versus celiac ganglia (R = 0.34, P < 0.0001), cervical versus sacral (R = 0.52, P < 0.0001), and celiac versus sacral (R = 0.16, P < 0.05). The 68Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, P < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, P < 0.0001; sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, P < 0.0001). Furthermore, ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) (P < 0.00001). Conclusion:68Ga-PSMA-ligand uptake in ganglia along the sympathetic trunk as assessed by 68Ga-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The 68Ga-PSMA-ligand uptake is higher in celiac ganglia than cervical or sacral ganglia, and the level of 68Ga-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic ganglia, both intensity of 68Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.

Comparison of 68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology.

PURPOSE: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared 68Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. METHODOLOGY: Seven patients with histopathologically proven primary PCa underwent 68Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sørensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. RESULTS: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57±22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (±0.18), 0.45 (±0.17) and 0.48 (±0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). CONCLUSION: In a slice by slice analysis with histopathology, 68Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.