Somatostatin receptor subtype expression and radiomics from DWI-MRI represent SUV of [68Ga]Ga-DOTATOC PET in patients with meningioma.

OBJECTIVE: This retrospective study aimed to analyse the correlation between somatostatin receptor subtypes (SSTR 1-5) and maximum standardized uptake value (SUVmax) in meningioma patients using Gallium-68 DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography ([68Ga]Ga-DOTATOC PET). Secondly, we developed a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUVmax. METHOD: The study included 51 patients who underwent MRI and [68Ga]Ga-DOTATOC PET before meningioma surgery. SUVmax values were quantified from PET images and tumour areas were segmented on post-contrast T1-weighted MRI and mapped to ADC maps. A total of 1940 radiomic features were extracted from the tumour area on each ADC map. A random forest regression model was trained to predict SUVmax and the model's performance was evaluated using repeated nested cross-validation. The expression of SSTR subtypes was quantified in 18 surgical specimens and compared to SUVmax values. RESULTS: The random forest regression model successfully predicted SUVmax values with a significant correlation observed in all 100 repeats (p < 0.05). The mean Pearson's r was 0.42 ± 0.07 SD, and the root mean square error (RMSE) was 28.46 ± 0.16. SSTR subtypes 2A, 2B, and 5 showed significant correlations with SUVmax values (p < 0.001, R2 = 0.669; p = 0.001, R2 = 0.393; and p = 0.012, R2 = 0.235, respectively). CONCLUSION: SSTR subtypes 2A, 2B, and 5 correlated significantly with SUVmax in meningioma patients. The developed radiomic model based on ADC maps effectively reproduces SUVmax using [68Ga]Ga-DOTATOC PET.

Anti-NMDA receptor encephalitis and MOG-associated demyelination - a case report with long-term follow-up and a systematic review.

BACKGROUND: Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics. CASE PRESENTATION: We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again. CONCLUSION: We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course.

Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy.

PURPOSE: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy. METHODS: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. RESULTS: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001). CONCLUSIONS: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients.

Impact of forced diuresis with furosemide and hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and kidneys on [68Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients.

PURPOSE: to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [68Ga]Ga-PSMA-11-PET/CT scans. MATERIALS AND METHODS: Comparison of four groups with 50 patients each, receiving different preparation prior to [68Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV). RESULTS: Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUVmean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUVmean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences). CONCLUSION: Performing [68Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.

The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

INTRODUCTION: A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in 177Lu-PSMA-617 radioligand therapy. METHODS: On the basis of PSMA-targeted 68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6-10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and 68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival. RESULTS: 177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 ± 2.64; range 1.10-13.00 Gy/GBq), lymph node (3.12 ± 2.07; range 0.70-8.70 Gy/GBq), and liver (2.97 ± 1.38; range 0.76-5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 ± 6.23 versus 12.33 ± 4.07) and submandibular glands (17.65 ± 7.34 versus 13.12 ± 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time. CONCLUSION: Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of 177Lu-PSMA-617-treated mCRPC patients whereas 68Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

Correction to: The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

The author name Bernhard Nilica was inadvertently interchanged in the original version of this article.

Organ-sparing surgery of penile cancer: higher rate of local recurrence yet no impact on overall survival.

PURPOSE: To report on the oncological outcome of organ-sparing surgery (OSS) compared to (total or partial) penectomy regarding recurrence patterns and survival in squamous cell carcinoma (SCC) of the penis. METHODS: This was a retrospective study of all patients with penile SCC and eligible follow-up data of at least 2 years at our institution. Patients with tumors staged ≥ pT1G2 underwent invasive lymph node (LN) staging by dynamic sentinel-node biopsy or modified inguinal lymphadenectomy. Radical inguinal lymphadenectomy was performed when LNs were palpable at diagnosis and in those with a positive LN status after invasive nodal staging. Follow-up visits were assessed, and local, regional and distant recurrences were defined and analyzed. RESULTS: 55 patients were identified with a mean follow-up of 63.7 months. Surgical management was OSS in 26 patients (47.2%) and partial or total penectomy in 29 cases (52.8%). Histopathological staging was: pTis (12.7%), pTa (16.3%), pT1a (18.2%), pT1b (5.5%), pT2 (29.1%) and pT3 (18.2%), respectively. Patients in the penectomy group were significantly older (mean 68 vs. 62 years; p = 0.026) with a higher rate of advanced tumor stage (≥ pT2: 44.8% vs. 11.5%; p = 0.002). The local recurrence rate was 42.3% (n = 11) following OSS compared to 10.3% (n = 3) after penectomy (p = 0.007). Kaplan-Meier curves showed no significant differences between the two groups regarding metastasis-free and overall survival. CONCLUSIONS: OSS is associated with a higher local recurrence rate compared to penectomy, yet it has no negative impact on overall and metastasis-free survival.

68Ga-PSMA-11 PET/CT: the rising star of nuclear medicine in prostate cancer imaging?

Ever since the introduction of 68Ga-prostate-specific membrane antigen 11 positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) a few years ago, it has rapidly achieved great success in the field of prostate cancer imaging. A large number of studies have been published to date, indicating a high potential of 68Ga-PSMA-11 PET/CT in the work-up of prostate cancer patients, including primary diagnosis, staging and biochemical recurrence. The aim of this review is to present the most important data on this novel, highly promising imaging technique, and to formulate recommendations for possible applications of 68Ga-PSMA-11 PET/CT in clinical routine.

Current status of theranostics in prostate cancer.

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of 68Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on 68Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for 68Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, 68Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. 68Ga-PSMA PET/CT is superior to 18F / 11Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of 177Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5-10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that 68Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as 223Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.

Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review.

AIMS: There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. RESULTS: Twelve studies including 669 patients reported 177Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177Lu-PSMA RLT. The treatment with 177Lu-PSMA-617 and 177Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ2 test). Median survival was longer after 177Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ2 test). CONCLUSIONS: As for patients with mCRPC, treatment with 177Lu-PSMA-617 RTL and 177Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.

Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy.

AIM: The purpose of this study was to investigate the diagnostic performance of 68Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [18F]sodium fluoride (18F-NaF) PET/CT. METHODS: Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18F-NaF PET and 68Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUVmax) and compared to background activity of normal bone. In addition, SUVmax values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. RESULTS: In contrast to 468 PET-positive lesions suggestive of bone metastases on 18F-NaF PET, only 351 of the lesions were also judged positive on 68Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18F-NaF PET compared to 68Ga-PSMA-11 PET, showing a median SUVmax of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68Ga-PSMA-11 PET, with a median SUVmax of 1.0 in comparison to 2.7 on 18F-NaF PET; however, tumour to background ratio was significantly higher on 18F-NaF PET (9.8 versus 5.9 on 68Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18F-NaF PET revealed median SUVmax values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68Ga-PSMA-11 PET median SUVmax values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between18F-NaF PET and 68Ga-PSMA-11 PET was significantly higher in osteosclerotic (p < 0.001) and lesions not visible on CT (p = 0.012). CONCLUSION: In comparison to 68Ga-PSMA-11 PET/CT, 18F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68Ga-PSMA-11 PET should be combined with 18F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates.

INTRODUCTION: A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Ten consecutive mCRPC patients were selected for 177Lu-PSMA617 therapy on the basis of PSMA-targeted 68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and 18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to 177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. RESULTS: 177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased 177Lu-PSMA617 and 68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. CONCLUSION: Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following 177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PURPOSE: PET/CT with 68Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. METHODS: Eighty consecutive PC patients referred to 68Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUVmax of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. RESULTS: A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suvmax was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. CONCLUSIONS: Early dynamic imaging in 68Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68Ga-PSMA-11 PET/CT.

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

PURPOSE: Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. METHODS: Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for 68Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax of the primary tumour was assessed in relation to both PSA level and GS. RESULTS: Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUVmax: 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68Ga-PSMA-11 uptake, with median SUVmax of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUVmax: 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUVmax: 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUVmax: 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUVmax: 11.6). CONCLUSIONS: The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on 68Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lower 68Ga-PSMA-11 uptake, 68Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS >7 or PSA levels ≥10 ng/ml.

Development of standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent lesions.

METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha<0.61]. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation. RESULTS: Between-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K's alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K's alpha: 0.64). K's alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written. CONCLUSION: We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PURPOSE: PET/CT using 68Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. METHODS: 203 consecutive PC patients with biochemical failure referred to 68Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUVmax) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. RESULTS: 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUVmax: 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUVmax: 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUVmax of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUVmax value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUVmax: 5.9 vs. 1.9, 4.0 and 2.4, respectively). CONCLUSIONS: Performance of early imaging in 68Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Influence of the anterior notch in mobile-bearing UKA on patellofemoral radiotracer uptake and clinical outcome.

BACKGROUND: Previous studies reported that in partial knee arthroplasty smooth transitions to the remaining native parts of the knee are important. However, in mobile-bearing unicondylar knee arthroplasty (UKA) it is mandatory to create an anterior osteochondral notch adjacent to the femoral component to get clearance for the anterior lip of the bearing in full knee extension. This notch is, however, part of the femoral trochlea. It was the aim of the study to test for a potential association between a) an obligatory anterior notch in mobile-bearing UKA located at the margin of the medial aspect of the femoral trochlea and b) postoperative patellofemoral joint (PFJ) bone remodelling and discomfort. METHODS: In patients who underwent routine mobile-bearing UKA (11 male, 13 female; 64.5 years / IQR 14) the following parameters were prospectively determined i) size of the surgically created anterior notch, ii) knee score sensitive to PFJ disorders, iii) bone remodelling in the PFJ (radiotracer uptake in SPECT-CT). RESULTS: Notch size was not correlated with radiotracer uptake at the PFJ. Similarly, no significant correlations were observed between radiotracer uptake (patella or trochleocondylar junction) and knee scores (KOOS or Kujala Score). Significant positive correlations were found between notch size and knee scores. CONCLUSIONS: From the findings made in our study it is concluded that a larger size of the anterior notch in mobile-bearing medial Oxford UKA is not associated with increased osteochondral remodelling processes at the patella or the trochleocondylar junction. Neither is a larger sized notch associated with worse clinical PFJ outcome. Surprisingly, a larger notch was even associated with superior clinical outcome. The exact mechanism for this contraintuitive finding remains unclear but may be the basis for future research. TRIAL REGISTRATION: The study is registered in a public trials registry. Link: (9/12/2017) ClinicalTrials.gov. NCT01407042 ; Date of registration: July, 26, 2011.