Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.
ABSTRACT: BACKGROUND:PET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared. RESULTS:PSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition. CONCLUSION:PSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes.
Project description:Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.
Project description:BACKGROUND:Prostate-specific membrane antigen (PSMA) ligand PET/CT has already provided promising results in prostate cancer (PC) imaging, yet simple and reproductible reporting criteria are still lacking. This study aimed at retrospectively evaluating interobserver agreement of [68Ga]Ga-PSMA-11 PET/CT images interpretation according to PC molecular imaging standardized evaluation (PROMISE) criteria and reproducibility of PSMA reporting and data systems (RADS). METHODS:Forty-three patients with newly diagnosed, histologically proven intermediate- or high-risk PC, eligible for radical prostatectomy and who underwent [68Ga]Ga-PSMA-11 PET/CT before surgery were retrospectively included. Three nuclear medicine physicians (2 experienced and 1 resident) independently reviewed PET/CT images. Interpretation of [68Ga]Ga-PSMA-11 PET/CT images was based on PROMISE criteria including miTNM staging and lesions miPSMA expression score visual estimation and PSMA-RADS version 1.0 for a given scan. Readers' agreement was measured using Krippendorff's coefficients RESULTS: Agreement between observers was almost perfect (coefficient ? 0.81) for miM; it was substantial (coefficient ? 0.61) for the following criteria: miT, miN, PSMA-RADS, and miPSMA expression score of primary PC lesion and metastases. However, agreement was moderate (coefficient = 0.41-0.60) for miPSMA score of positive lymph nodes and for detection of PC primary lesion. CONCLUSION:Visual interpretation of [68Ga]Ga-PSMA-11 PET/CT images in patients with newly diagnosed PC in a clinical setting leads to at least substantial agreement for PROMISE criteria and PSMA-RADS classification except for PC primary lesion detection and for miPSMA expression scoring of positive lymph nodes that might have been hampered by the interindividual variability of reference organs PSMA expression.
Project description:We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.
Project description:The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, 68Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of 18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of 18F-PSMA-1007 in human volunteers and patients.Radiation dosimetry of 18F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent 18F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining.With an effective dose of approximately 4.4-5.5 mSv per 200-250 MBq examination, 18F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to 18F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2-3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. 18F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.18F-PSMA-1007 performs at least comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of 68Ga-labelled PSMA-targeted tracers.
Project description:18F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to 68Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their 68Ga-labeled counterparts. Here, we describe the efficacy of an 18F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Methods: Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent 18F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients' prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). Results: The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01-400 ng/mL). The median injected activity of 18F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on 18F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ?2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. 18F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, P = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, P = 0.54), or primary Gleason score (77.9% for ?7 vs. 82.6% for ?8, P = 0.38). Conclusion: 18F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.
Project description:Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ?20 ng/mL, 41%; P < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score (P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level (P < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Conclusion: Bone metastases as assessed with 68Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because 68Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in 68Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management.
Project description:Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists' assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, "learning" the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance.
Project description:PURPOSE:Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression. Therefore, we hypothesised that ADT improves the performance of PSMA-PET imaging in primary staging of prostate cancer. The purpose of the study was to demonstrate the time course effect of ADT on PSMA uptake in different types of metastatic lesions evaluated with 68Ga-PSMA-11 PET/MRI. METHODS:Nine men with treatment-naïve prostate cancer were enrolled to a prospective, registered (NCT03313726) clinical trial. A 68Ga-PSMA-11 PET/MRI was performed once before and 3 times post-ADT (degarelix, Firmagon). Change of maximum standardised uptake values (SUVmax) in prostate, lymph nodes, bone metastases, and physiologically PSMA-avid organs were evaluated in a time frame of 1-8 weeks. RESULTS:All patients reached castration levels within 10 days, and 50% decrease in prostate-specific antigen (PSA) concentration was observed 14 days post-ADT. A heterogeneous increase in PSMA uptake was observed 3 to 4 weeks post-ADT. This phenomenon was definitively more evident in bone metastases: 13 (57%) of the metastasis, with a mean (range) SUVmax increase of 77% (8-238%). In one patient, already having bone metastases at baseline, three new bone metastases were observed post-ADT. Of lesions with reduced SUVmax, none disappeared. CONCLUSIONS:Both in patient and region level, increase in PSMA uptake post-ADT is heterogenous and is seen most evidently in bone metastases. Preliminary results on a small cohort of patients suggest the clinical impact of ADT on improving the performance of 68Ga-PSMA PET in staging seems to be minor. However, the optimal imaging time point might be 3 to 4 weeks post-ADT. Since none of the metastases with decreasing SUVmax disappeared, it seems that short-term usage of ADT does not interfere with the interpretation of 68Ga-PSMA PET. TRIAL REGISTRATION:NCT03313726, registered 18 October 2017; EUDRA-CT, 2017-002345-29.
Project description:PURPOSE:Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemically recurrent prostate cancer (BCR), mostly using gallium-68 (168Ga)-labelled radiotracers. Alternatively, fluorine-18 (18F)-labelled PSMA tracers are available, such as 18F-DCFPyL, which offer enhanced image quality and therefore potentially increased detection of small metastases. In this study we evaluate the lesion detection efficacy of 18F-DCFPyL PET/CT in patients with BCR and determine the detection efficacy as a function of their PSA value. METHODS:A total of 248 consecutive patients were evaluated and underwent scanning with 18F-DCFPyL PET/CT for BCR between November 2016 and 2018 in two hospitals in the Netherlands. Patients were examined after radical prostatectomy (52%), external-beam radiation therapy (42%) or brachytherapy (6%). Imaging was performed 120 min after injection of a median dose of 311 MBq 18F-DCFPyL. RESULTS:In 214 out of 248 PET/CT scans (86.3%), at least one lesion suggestive of cancer recurrence was detected ('positive scan'). Scan positivity increased with higher PSA values: 17/29 scans (59%) with PSA values <0.5 ng/ml; 20/29 (69%) with PSA 0.5 to <1.0 ng/ml; 35/41 (85%) with PSA 1.0 to <2.0 ng/ml; 69/73 (95%) with PSA 2.0 to <5.0 ng/ml; and 73/76 (96%) with PSA ≥5.0 ng/ml. Interestingly, suspicious lesions outside the prostatic fossa were detected in 39-50% of patients with PSA <1.0 ng/ml after radical prostatectomy (i.e. candidates for salvage radiotherapy). CONCLUSION:18F-DCFPyL PET/CT offers early detection of lesions in patients with BCR, even at PSA levels <0.5 ng/ml. These results appear to be comparable to those reported for 68Ga-PSMA and 18F-PSMA-1007, with potentially increased detection efficacy compared to 68Ga-PSMA for patients with PSA <2.0.
Project description:PURPOSE:To assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). PATIENTS AND METHODS:In a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND. RESULTS:The median age of the patients at the time of SLND was 65 years (IQR 63-69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8-2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33-48) and the median number of positive nodes was 4 (IQR 2-6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3-9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1-5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively. CONCLUSION:PSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.