Robotic Retroperitoneal Versus Transperitoneal Partial Nephrectomy: Outcomes and Learning Curve.

BACKGROUND/AIM: The robotic retroperitoneal approach for renal mass surgery was introduced in 2018 at the Department of Urology in the clinic of Leverkusen, Germany. Clinical criteria for the choice of the access site (trans- vs. retroperitoneal) are not clearly defined. The aim of this study was to explore the learning curve and the impact of the access site on clinical outcome, in order to elucidate which preoperative clinical criteria should be taken into account when choosing the renal approach site. PATIENTS AND METHODS: This retrospective study included 107 patients who underwent robotic tumor surgery between June 2018 and March 2022 at the Department of Urology in the Clinic of Leverkusen, Germany. Data from 86 patients with transperitoneal robotic surgery of the kidney and 21 patients with retroperitoneal access were available for analysis. We evaluated the data of patients in a trans- and a retroperitoneal access group. The preoperative clinical data included anthropomorphic data, the Body Mass Index (BMI) as well as the Preoperative Aspects and Dimensions Used for Anatomical Classification of Renal Masses (PADUA) - score. Intraoperative and postoperative data such as blood loss, clamping time, renal function and the learning curve of the surgeons was used to evaluate the outcomes of the two groups. RESULTS: Operation time in the retroperitoneal group was significantly shorter (p=0.015). Operation-specific variables showed no significant difference between the two groups. PADUA score and hilar clamping time showed no difference (p=0.345 and p=0.130, respectively). The learning curve in the retroperitoneal access group unveiled a noticeable difference in the experience and mastery of the involved surgeons. CONCLUSION: Mastery of the retroperitoneal approach is readily possible for surgeons with previous experience in robotic renal surgery without compromising the operative morbidity. The PADUA-score seems most suitable as a preoperative clinical criterion for choosing the renal approach site.

Detection Efficacy of 68Ga-PSMA-11 PET/CT in Biochemical Recurrence of Prostate Cancer with Very Low PSA Levels: A 7-Year, Two-Center "Real-World" Experience.

In biochemical recurrence of prostate cancer (BCR), prompt tumor localization guides early treatment, potentially improving patient outcomes. Gallium-68 prostate-specific membrane antigen-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) detection rates of lesions suspicious for prostate cancer are well known to rise along with prostate-specific antigen (PSA) concentration. However, published data are limited regarding very low values (≤0.2 ng/mL). We retrospectively analyzed ~7-year "real-world" experience in this setting in a large post-prostatectomy cohort (N = 115) from two academic clinics. Altogether 44 lesions were detected in 29/115 men (25.2%) (median [minimum-maximum] 1 [1-4]/positive scan). The apparent oligometastatic disease was found in nine patients (7.8%) at PSA as low as 0.03 ng/mL. Scan positivity rates were highest when PSA was >0.15 ng/mL, PSA doubling time was ≤12 months, or the Gleason score was ≥7b (in 83 and 107 patients, respectively, with available data); these findings were statistically significant (p ≤ 0.04), except regarding PSA level (p = 0.07). Given the benefits of promptly localizing recurrence, our observations suggest the potential value of 68Ga-PSMA-11 PET/CT in the very low PSA BCR setting, especially in cases with more rapid PSA doubling time or with high-risk histology.

Prediction of Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging Lesions: A High-volume International Multicenter Study.

BACKGROUND: Decision of performing prostate biopsy in men with Prostate Imaging Reporting and Data System (PI-RADS) 3 findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). OBJECTIVE: To identify clinical predictors of sPC in men with PI-RADS 3 lesions in prostate MRI and to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a retrospective multinational cohort from ten academic centers comprising 1476 men who underwent a combined prostate biopsy (MRI targeted plus systematic biopsy) between February 2012 and April 2021 due to a PI-RADS 3 lesion in prostate MRI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the detection of sPC (ISUP ≥2) in a combined biopsy. Predictors were identified by a regression analysis. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. RESULTS AND LIMITATIONS: Of all patients, 273/1476 (18.5%) were diagnosed with sPC. MRI-targeted biopsy diagnosed fewer sPC cases than combined strategy: 183/1476 (12.4%) versus 273/1476 (18.5%), p < 0.01. Age (odds ratio [OR] 1.10 [95% confidence interval {CI}: 1.05-1.15], p < 0.001), prior negative biopsy (OR 0.46 [0.24-0.89], p = 0.022), and PSAD (p < 0.001) were found to be independent predictors of sPC. Applying a PSAD cutoff of 0.15, 817/1398 (58.4%) biopsies would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period, and no central revision of MRI. CONCLUSIONS: Age, previous biopsy status, and PSAD were found to be independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting. PATIENT SUMMARY: In this study, we looked for clinical predictors of significant prostate cancer in men with Prostate Imaging Reporting and Data System 3 lesions in prostate magnetic resonance imaging. We identified age, previous biopsy status, and especially prostate-specific antigen density as independent predictors.

Efficacy of cabazitaxel in fourth or later line of therapy in metastatic castration-resistant prostate cancer: Multi-institutional real-world experience in Germany.

OBJECTIVE: Since multiple oncological treatment options in metastatic castration-resistant prostate cancer (mCRPC) are available, optimal sequencing of therapies are under investigation. However, the efficacy of Cabazitaxel (CAB) in fourth and later lines of therapy is rarely investigated. MATERIAL AND METHODS: Fifty three patients with mCRPC treated with CAB in fourth line or later were included in our retrospective study, which involved eight uro-oncology centers in Germany. Clinical and tumor characteristics, as well as PSA-response rates were analyzed. Kaplan-Meier plots addressed overall survival (OS) and progression-free survival (PFS). Logistic regression models predicted risk factors of overall mortality (OM). RESULTS: Of 53 patients, 79% (n=42), 19% (n=10) and 2% (n=1) received CAB in fourth, fifth and sixth line. A median of 4 cycles of CAB were administered. Median PSA at start of CAB was 199ng/ml (interquartile range (IQR) 70-869). In total, 89% had bone and 40% visceral metastases prior to the start of CAB. Moreover, 30% of patients received Docetaxel in first line therapy for mCRPC. Most frequent sequence of therapy was abiraterone followed by docetaxel and followed by enzalutamide. Overall, median PSA-response rate was -20% (IQR -80 to +10%). Patients with docetaxel in first line had a significantly better median PSA-response on CAB (-80 vs. 20%, P=0.03). Median OS, radiographic PFS and overall PFS were 14.8 (Confidence interval (CI): 11.0-20.8), 3.0 (CI: 2.9-4.0) and 2.9 (CI: 2.0-3.3) months, respectively. In multivariable analyses, visceral metastases, PSA >100ng/ml, ISUP4+5 and later administration of Docetaxel were predictors of OM. CONCLUSION: Real-world experiences indicate that favorable oncologic outcomes can be achieved with CAB especially regarding PSA-response and OS even in the fourth line or later in patients with mCRPC.

Primary Staging of Prostate Cancer Patients with [18F]PSMA-1007 PET/CT Compared with [68Ga]Ga-PSMA-11 PET/CT.

BACKGROUND: Hybrid imaging with prostate-specific membrane antigen (PSMA) is gaining importance as an increasingly meaningful tool for prostate cancer (PC) diagnostics and as a guide for therapy decisions. This study aims to investigate and compare the performance of [18F]PSMA-1007 (18F-PSMA) and [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA) in the initial staging of PC patients. METHODS: The data of 88 biopsy-proven patients were retrospectively evaluated. PSMA-avid lesions were compared with the histopathologic Gleason Score (GS) for prostate biopsies, and the results were plotted by receiver operating characteristic (ROC)-curve. Optimal maximum standardized uptake value (SUVmax) cut-off values were rated using the Youden index. RESULTS: 18F-PSMA was able to distinguish GS ≤ 7a from ≥7b with a sensitivity of 62%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 67% for a SUVmax of 8.95, whereas sensitivity was 54%, specificity 91%, PPV 93%, and accuracy 66% for 68Ga-PSMA (SUVmax 8.7). CONCLUSIONS: Both methods demonstrated a high concordance of detected PSMA-avid lesions with histopathologically proven PC. 18F-PSMA and 68Ga-PSMA are both suitable for the characterization of primary PC with a comparable correlation of PSMA-avid lesions with GS. Neither method showed a superior advantage. Our calculated SUVmax thresholds may represent valuable parameters in clinical use to distinguish clinically significant PC (csPC) from non-csPC.

Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC.

In this study, we investigated upregulation of prostate-specific membrane antigen (PSMA) by enzalutamide in a cohort (n = 30) of patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Patients were examined by [68Ga]Ga-PSMA-11 PET/CT pre- and post-enzalutamide medication (mean 13 ± 7 days). Imaging results were compared based on quantification of whole-body PSMA tumor burden: total lesion PSMA (TLP) and normalized TLP values to liver (TLP-LR) and to parotid gland (TLP-PR). In addition, lesion-based analyses were performed. The median (mean) increases in TLP, TLP-LR and TLP-PR after enzalutamide medication were 10.1% (20.2%), 29.5% (34.8%) and 27.6% (24.4%), respectively. These increases were statistically significant (p = 0.002, p < 0.001, and p < 0.001), while prostate-specific antigen (PSA) serum values did not change significantly (p = 0.483). The increase was independent of prior patient exposure to enzalutamide. SUVmax increased substantially (>10%) in 49.6% of target lesions. The relative change was significantly higher in the subgroup of lesions with SUVmax < 10 (p < 0.001). In conclusion, short-term enzalutamide medication significantly increases PSMA expression in patients with mCRPC, irrespective of prior enzalutamide exposure. The relative PSMA upregulation effect seems to be more pronounced in lesions with only moderate baseline PSMA expression. Enzalutamide may provide a potential enhancer medication for PSMA-targeted radioligand therapy.

Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse.

This study aimed to compare the diagnostic performance of [18F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (18F-PSMA) and [68Ga]Ga-PSMA-11 PET/CT (68Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of 18F-PSMA and 68Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. 18F-PSMA showed PC-lesions in 87.5% (112/128 patients), while 68Ga-PSMA identified them in 88.9% (121/136). For 18F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710−0.932), while for prostatectomized 68Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410−0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for 18F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to 68Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings.

Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy.

PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. METHODS: Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. RESULTS: By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). CONCLUSION: The new whole-body molecular imaging-derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.

mRNA and small RNA gene expression changes in peripheral blood to detect internal Ra-223 exposure.

PURPOSE: Excretion analysis is the established method for detection of incorporated alpha-emitting radionuclides, but it is laborious and time consuming. We sought a simplified method in which changes in gene expression might be measured in human peripheral blood to detect incorporated radionuclides. Such an approach could be used to quickly determine internal exposure in instances of a radiological dispersal device or a radiation accident. MATERIALS AND METHODS: We evaluated whole blood samples from five patients with castration-resistant prostate cancer and multiple bone metastases (without visceral or nodal involvement), who underwent treatment with the alpha emitting isotope Radium-223 dichloride (Ra-223, Xofigo®). Patients received about 4 MBq per cycle and, depending on survival and treatment tolerance, were followed for six months. We collected 24 blood samples approximately monthly corresponding to treatment cycle. RESULTS: Firstly, we conducted whole genome screening of mRNAs (mRNA seq) and small RNAs (small RNA seq) using next generation sequencing in one patient at eight different time points during all six cycles of Ra-223-therapy. We identified 1900 mRNAs and 972 small RNAs (222 miRNAs) that were differentially up- or down-regulated during follow-up after the first treatment with Ra-223. Overall candidate RNA species inclusion criteria were a general (≥|2|-fold) change or with peaking profiles (≥|5|-fold) at specific points in time. Next we chose 72 candidate mRNAs and 101 small RNAs (comprising 29 miRNAs) for methodologic (n = 8 samples, one patient) and independent (n = 16 samples, four patients) validation by qRT-PCR. In total, 15 mRNAs (but no small RNAs) were validated by methodologic and independent testing. However, the deregulation occurred at different time points, showing a large inter-individual variability in response among patients. CONCLUSIONS: This proof of concept provides support for the applicability of gene expression measurements to detect internalized alpha-emitting radionuclides, but further work is needed with a larger sample size. While our approach has merit for internal deposition monitoring, it was complicated by the severe clinical condition of the patients we studied.

Active surveillance inclusion criteria under scrutiny in magnetic resonance imaging-guided prostate biopsy: a multicenter cohort study.

BACKGROUND: Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. METHODS: A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. RESULTS: Of 1941 patients with PCa, per guideline, 583-1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4-72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7-68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. CONCLUSIONS: Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria.

Age- and Sex-Graded Data Evaluation of Vaccination Reactions after Initial Injection of the BNT162b2 mRNA Vaccine in a Local Vaccination Center in Germany.

A high vaccination rate of older and particularly chronically ill people against coronavirus disease-2019 (COVID-19) is likely one of the most important factors in containing the pandemic. When Germany's vaccination campaign started on December 2020, vaccination prioritization was initially carried out starting with older population groups. Side effect rates in 1065 individuals who had received the first dose of the messenger ribonucleic acid (mRNA) vaccine BNT162b2 Tozinameran from BioNTech/Pfizer three weeks earlier were examined retrospectively. An age- and gender-graded data analysis showed clear age and gender differences with regard to vaccine-related adverse effects. In 77% of all individuals over 80 years of age, no local or systemic side effects were reported after the first vaccination, whereas in the age group up to 80 years, only 37% showed no side effects. In the whole study population, 64% of females and 73% of males reported no adverse effects. The initial vaccination with mRNA vaccine BNT162b2 shows an overall low profile of side effects. Particularly in those over 80 years, an extraordinarily good tolerance with equally good effectiveness is evident. The sex comparison showed that women suffer more often from adverse vaccination reactions. In order to achieve sufficient herd immunity, both age- and gender-dependent vaccination reactions and any difference in the maintenance of immunity should be considered in future vaccination strategies.

Impact of prompt gamma emission of 44Sc on quantification in preclinical and clinical PET systems.

44Sc is an increasingly investigated positron emitter for use in positron emission tomography (PET) imaging. However, 44Sc is a non-pure positron emitter, since prompt photons are co-emitted during the decay process. This study investigates coincidence energy spectra of 44Sc and its impact on PET quantification on a preclinical and clinical PET system in comparison with 18F. The raw data of the coincidence events revealed characteristic differences comparing the photon energy distribution of 44Sc and 18F. Due to prompt gamma emission of 44Sc, activity recovery is underestimated on PET systems. However, clinical PET imaging of 44Sc with acceptable quantitative accuracy appears feasible by using a single, constant correction factor.

Acceptance, Indications and Chances of Focal Therapy in Localized Prostate Cancer: A Real-World Perspective of Urologists in Germany.

Purpose: Focal therapy (FT) became a frequently discussed treatment strategy of localized prostate cancer (PCa), but the acceptance and evaluation of FT by practicing urologists are still unclear. Methods: A 25-item anonymized online questionnaire (SurveyMonkey®) was compiled by the German Society of Residents in Urology Academics Prostate Cancer Working Group and sent to the members of the German association of Urology. Logistic regression analysis was performed to determine parameters for suggestion FT. Results: Two hundred ten urologists (median age 49 years) participated, from which 72% stated PCa as their main treatment focus. Ninety-nine percent of urologists were aware of and 54% wanted to improve their knowledge about FT. Sixty-five percent do not treat PCa with FT. FT is seen as an alternative to active surveillance and radiotherapy/radical prostatectomy by 66% and 37%, respectively. Regarding FT treatment strategies, 35% and 45% would treat all or all significant PCa foci, respectively, whereas 19% would treat mainly the index foci. Currently, 27% believe that FT will be an option as standard treatment in future, but 48% would not suggest FT to their patients, owing to an absence of evidence and insufficient diagnostic tools for proper patient selection today. Suggesting FT to patients is associated with self-performing FT (odds ratio [OR] 2.88, 95% confidence interval [CI] 1.31-6.31) and believing in FT as a standard treatment in future (OR 9.05, 95% CI 6.68-22.30) (both p < 0.01). Conclusion: FT has currently no wide acceptance in German practicing urologists, mainly attributable to an absence of evidence for FT superiority compared to standard treatments.

Quantification of the Cannabinoid Type 1 Receptor Availability in the Mouse Brain.

Introduction: The endocannabinoid system is involved in several diseases such as addictive disorders, schizophrenia, post-traumatic stress disorder, and eating disorders. As often mice are used as the preferred animal model in translational research, in particular when using genetically modified mice, this study aimed to provide a systematic analysis of in vivo cannabinoid type 1 (CB1) receptor ligand-binding capacity using positron emission tomography (PET) using the ligand [18F]MK-9470. We then compared the PET results with literature data from immunohistochemistry (IHC) to review the consistency between ex vivo protein expression and in vivo ligand binding. Methods: Six male C57BL/6J (6-9 weeks) mice were examined with the CB1 receptor ligand [18F]MK-9470 and small animal PET. Different brain regions were evaluated using the parameter %ID/ml. The PET results of the [18F]MK-9470 accumulation in the mouse brain were compared with immunohistochemical literature data. Results: The ligand [18F]MK-9470 was taken up into the mouse brain within 5 min after injection and exhibited slow kinetics. It accumulated highly in most parts of the brain. PET and IHC classifications were consistent for most parts of the telencephalon, while brain regions of the diencephalon, mesencephalon, and rhombencephalon were rated higher with PET than IHC. Conclusions: This preclinical [18F]MK-9470 study demonstrated the radioligand's applicability for imaging the region-specific CB1 receptor availability in the healthy adult mouse brain and thus offers the potential to study CB1 receptor availability in pathological conditions.

Dual-Time Point [68Ga]Ga-PSMA-11 PET/CT Hybrid Imaging for Staging and Restaging of Prostate Cancer.

Routine [68Ga]Ga-PSMA-11 PET/CT (one hour post-injection) has been shown to accurately detect prostate cancer (PCa) lesions. The goal of this study is to evaluate the benefit of a dual-time point imaging modality for the staging and restaging of PCa patients. Biphasic [68Ga]Ga-PSMA-11 PET/CT of 233 patients, who underwent early and late scans (one/three hours post-injection), were retrospectively studied. Tumor uptake and biphasic lesion detection for 215 biochemically recurrent patients previously treated for localized PCa (prostatectomized patients (P-P)/irradiated patients (P-I) and 18 patients suspected of having primary PCa (P-T) were separately evaluated. Late [68Ga]Ga-PSMA-11 PET/CT imaging detected 554 PCa lesions in 114 P-P patients, 187 PCa lesions in 33 P-I patients, and 47 PCa lesions in 13 P-T patients. Most patients (106+32 P-P/P-I, 13 P-T) showed no additional PCa lesions. However, 11 PSMA-avid lesions were only detected in delayed images, and 33 lesions were confirmed as malignant by a SUVmax increase. The mean SUVmax of pelvic lymph node metastases was 25% higher (p < 0.001) comparing early and late PET/CT. High positivity rates from routine [68Ga]Ga-PSMA-11 PET/CT for the staging and restaging of PCa patients were demonstrated. There was no decisive influence of additional late imaging with PCa lesion detection on therapeutic decisions. However, in a few individual cases, additional delayed scans provided an information advantage in PCa lesion detection due to higher tracer uptake and improved contrast.

Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma.

Gallium-68 (Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with Ga-prostate-specific-membrane-antigen-11 were evaluated retrospectively. Prostate-specific-antigen-stratified cohorts of pathological scan results were analyzed, and relationships between prostate-specific-antigen kinetics and PSMA-positive tumor lesions were correlated. Gallium-68 prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography showed a pathological prostate-specific-membrane-antigen uptake in 76% (500 of 660 patients). Positive scans were positively associated with prostate-specific-antigen (p<0.001). For patients with prostate-specific-antigen <0.2 ng mL, the PSMA-positive tumor lesions rate was 41%. Patients with prostate-specific-antigen of 0.2-<0.5 ng mL, 0.5-<1.0 ng mL, 1.0-<2.0 ng mL, and 2.0-<5.0 ng mL showed rates of 44.7%, 61.7%, 72.3%, 85.2%, respectively, and for prostate-specific-antigen of ≥5.0 ng mL it increased to 94%. Prostate-specific-antigen velocity was also correlated with PSMA-positive tumor lesions (p<0.001). In contrast, no association was found for prostate-specific-antigen doubling time (p=0.74). PSMA-positive tumor lesions were significantly increased in patients with primary intermediate- (Gleason Score7) and high-risk (Gleason Score>7) vs. low-risk prostate cancer (Gleason Score<7) (p<0.001). Our data confirm the high performance of Ga-prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography for the detection of recurrent prostate cancer. This may alter treatment planning and has been documented in other studies as well.

Image quality analysis of 44Sc on two preclinical PET scanners: a comparison to 68Ga.

BACKGROUND: 44Sc has been increasingly investigated as a potential alternative to 68Ga in the development of tracers for positron emission tomography (PET). The lower mean positron energy of 44Sc (0.63 MeV) compared to 68Ga (0.83 MeV) can result in better spatial image resolutions. However, high-energy γ-rays (1157 keV) are emitted at high rates (99.9%) during 44Sc decay, which can reduce image quality. Therefore, we investigated the impact of these physical properties and performed an unbiased performance evaluation of 44Sc and 68Ga with different imaging phantoms (image quality phantom, Derenzo phantom, and three-rod phantom) on two preclinical PET scanners (Mediso nanoScan PET/MRI, Siemens microPET Focus 120). RESULTS: Despite the presence of high-energy γ-rays in 44Sc decay, a higher image resolution of small structures was observed with 44Sc when compared to 68Ga. Structures as small as 1.3 mm using the Mediso system, and as small as 1.0 mm using the Siemens system, could be visualized and analyzed by calculating full width at half maximum. Full widths at half maxima were similar for both isotopes. For image quality comparison, we calculated recovery coefficients in 1-5 mm rods and spillover ratios in either air, water, or bone-equivalent material (Teflon). Recovery coefficients for 44Sc were significantly higher than those for 68Ga. Despite the lower positron energy, 44Sc-derived spillover ratio (SOR) values were similar or slightly higher to 68Ga-derived SOR values. This may be attributed to the higher background caused by the additional γ-rays. On the Siemens system, an overestimation of scatter correction in the central part of the phantom was observed causing a virtual disappearance of spillover inside the three-rod phantom. CONCLUSION: Based on these findings, 44Sc appears to be a suitable alternative to 68Ga. The superior image resolution makes it an especially strong competitor in preclinical settings. The additional γ-emissions have a small impact on the imaging resolution but cause higher background noises and can effect an overestimation of scatter correction, depending on the PET system and phantom.

The positivity rate of 68Gallium-PSMA-11 ligand PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-<0.5 ng/ml the PR was 45%, 62% for PSAV of 0.5-<1.0 and 72% for PSAV of 1.0-<2.0 ng/ml. The PR increased to 85% for PSAV of 2.0-<5.0 and reached 94% at PSAV of ≥5.0 ng/ml. At PSA of <1 ng/ml/y the PR of PSAvel was 50% and increased to 98% at PSA >5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (<0.2 ng/ml). Thus 68Ga-PSMA-11 PET/CT both identify and localize recurrent disease with implications for a more direct treatment approach (localized vs. systemic therapy).

18F-FDG PET/CT: an unexpected case of Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a rare, genetic neurodegenerative disorder often presenting with emotional, cognitive and behavioral abnormalities before manifestation of disease defining motor symptoms. Cognitive impairment is a frequent clinical feature caused by different dementia subtypes. Imaging cortical and subcortical glucose metabolism via 18F-FDG PET/CT can help to discriminate the underlying disease. CASE PRESENTATION: The patient is a 54-year old man presenting with progressive cognitive impairment and mild orofacial dyskinesia. 18F-FDG PET/CT of the brain revealed a severe bilateral hypometabolism in the striatum. Following imaging Huntington's disease was suspected and a molecular genetic testing confirmed the diagnosis. CONCLUSIONS: Huntington's disease is a rare but important differential diagnosis of cognitive impairment, especially before motor symptoms are manifest. 18F-FDG PET is capable to show early striatal dysfunction in HD even when structural imaging is normal. We conclude that, in cases with negative family history the HD characteristic metabolic pattern can lead to the diagnosis when no other dementia-suspected changes are present.