Influence of short-term dexamethasone on the efficacy of 177 Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer.

BACKGROUND AND AIM: Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with 177 Lu-prostate-specific membrane antigen (PSMA)-617. PATIENTS AND METHODS: Seventy-one patients with mCRPC were treated with 1 to 5 cycles of 177 Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT. RESULTS: PSA response rates were not significantly different between patients receiving 177 Lu-PSMA-617 plus dexamethasone and those receiving 177 Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (-21% ± 50% vs +11% ± 90%, P = .08; -21% ± 69% vs +22% ± 116%, P = .07; -13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving 177 Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases. CONCLUSIONS: We observed high response rates to 177 Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to 177 Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.

Fermentative hydrogen production from low-value substrates.

Hydrogen is a promising energy source that is believed to replace the conventional energy sources e.g. fossil fuels over years. Hydrogen production methods can be divided into conventional production methods which depend mainly on fossil fuels and alternative production methods including electrolysis of water, biophotolysis and fermentation hydrogen production from organic waste materials. Compared to the conventional methods, the alternative hydrogen production methods are less energy intensive and negative-value substrates i.e. waste materials can be used to produce hydrogen. Among the alternative methods, fermentation process including dark and photo-fermentation has gained more attention because these processes are simple, waste materials can be utilized, and high hydrogen yields can be achieved. The fermentation process is affected by several parameters such as type of inoculum, pH, temperature, substrate type and concentration, hydraulic retention time, etc. In order to achieve optimum hydrogen yields and maximum substrate degradation, the operating conditions of the fermentation process must be optimized. In this review, two routes for biohydrogen production as dark and photo-fermentation are discussed. Dark/photo-fermentation technology is a new approach that can be used to increase the hydrogen yield and improve the energy recovery from organic wastes.

PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

PURPOSE: [68Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68Ga3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68Ge/68Ga-generator. We evaluated the clinical detection rates of [68Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS: Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [68Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. RESULTS: At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [68Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [68Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [68Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). CONCLUSIONS: In this study, [68Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands.

Imaging Characteristics and First Experience of [68Ga]THP-PSMA, a Novel Probe for Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with [68Ga]PSMA I&T.

PURPOSE: [68Ga]Trishydroxypyridinone (THP)-prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [68Ga]THP-PSMA. PROCEDURES: [68Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [68Ga]PSMA I&T. RESULTS: Physiologic uptake of [68Ga]THP-PSMA was significantly lower in salivary glands (P < 0.0001), liver (P < 0.0001), spleen (P < 0.0001), and kidneys (P < 0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T. CONCLUSION: [68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [68Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.

Screening of extravascular findings in pulmonary embolism computer tomography: 397 patients with 1950 non-pulmonary artery findings.

Objectives The aim of this study was to investigate the possible benefits from computed tomography scans of patients with a suspected pulmonary artery embolism with a focus on relevant extravascular findings. Methods A total of 400 consecutive computed tomography pulmonary angiographies were evaluated. Computed tomography scans were analyzed in detail for the presence of pulmonary artery embolisms, as well as any other findings. Extra-artery discoveries were classified into none-relevant (Group A), intermediate (Group B), or relevant (Group C) findings. Results Aggregated computed tomography pulmonary angiographies detected other diagnosis than pulmonary artery embolism in 236 patients (59%). There were 1950 non-pulmonary artery embolism findings (4.9 per patient; n = 397). In the pulmonary artery embolism group, there were 447 extra-pulmonary artery embolism findings (5.2 per patient; n = 86) and in the non-pulmonary artery embolism group, 1503 findings (4.8 per patient; n = 311). Patients with pulmonary artery embolism had a significantly higher rate of pro-coagulate risk factors ( p < 0.001). Conclusions Computed tomography pulmonary angiographies may help to identify further diagnoses. This study represents a retrospective review of a single center experience for incidental computed tomography findings during pulmonary artery embolism work-up and emphasizes the importance of analyzing the whole field-of-view.

Extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities: A retrospective study of 352 patients.

Background The aim of this study was to assess the prevalence and clinical significance of extra-vascular findings in patients undergoing magnetic resonance angiography of the abdomen, pelvis and lower extremities. Materials and methods Three hundred fifty-two patients underwent abdominal, pelvic and lower extremity 1.5 T magnetic resonance angiography. Clinically relevant vascular and extra-vascular findings were identified. Relevant vascular findings were classified as stenosis, occlusion, aneurysm, sclerosis, dissection or vasculitis. Relevant extra-vascular findings were categorized as 'safe' (Group A), intermediate - requiring additional investigation - (Group B) and malignant/endangering - requiring change of therapy (Group C). Results A total of 2152 clinically relevant vascular findings was identified (6.1/patient). The most frequent vascular finding was femoral artery stenosis (10.6%). Four hundred fifty-one extra-vascular findings were observed (1.3/patient) and classified into Group A (78%), Group B (19.5%) and Group C findings (2.4%). The most frequent malignant findings were lung cancer, lymphoma, osteosarcoma, hepatocellular carcinoma and renal cell carcinoma (7/352 patients). Conclusions Extravascular findings are frequently encountered in magnetic resonance angiography performed for vascular indications. Clinically relevant findings are seen in a substantial part of patients and should prompt further diagnostic work-up.

68Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent, Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer.

PURPOSE: 68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) has shown promising results in patients with biochemical recurrence after primary therapy for prostate cancer. In this study, we evaluated the usefulness of PSMA I&T (imaging and therapy) PET/CT prior to radical prostatectomy. METHODS: The study population consisted of 21 patients with prostate cancer who underwent 68Ga-PSMA I&T PET/CT before either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were assessed on the PET/CT scans. Tracer uptake was quantified in terms of standardized uptake values (SUVs). Imaging findings were correlated with final whole-gland histopathology. RESULTS: Of the 21 patients, two had T stage 2b disease, nine stage 2c, six stage 3a and four stage 3b. The median Gleason score was 7. The SUVmean of the primary tumors was 9.5 ± 8.8. SUVmean was higher in tumors with ECE than in organ-confined tumors (13.8 ± 11.0 vs. 5.6 ± 3.2, p = 0.029). Peak tracer uptake was significantly positively correlated with Gleason score (rs = 0.49, p = 0.025). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 94.7%, 75.0%, 97.3% and 60.0% for tumor infiltration of an individual prostate lobe, 75.0%, 100.0%, 100.0% and 97.4% for SVI, and 90.0%, 90.9%, 90.0% and 90.9% for ECE, using an angulated contour of the prostate as the criterion. Tumor volume derived from 68Ga-PSMA I&T PET/CT was significantly correlated with preoperative prostate-specific antigen value (rp = 0.75, p < 0.001) and tumor volume on histopathology (rp = 0.45, p = 0.039). CONCLUSIONS: 68Ga-PSMA I&T PET/CT prior to radical prostatectomy can contribute to presurgical local staging of prostate cancer. In this pilot study, 68Ga-PSMA I&T PET/CT showed promising results for prediction of lobe infiltration, ECE and SVI.

Initial Experience with Volumetric 68Ga-PSMA I&T PET/CT for Assessment of Whole-Body Tumor Burden as a Quantitative Imaging Biomarker in Patients with Prostate Cancer.

A quantitative imaging biomarker is desirable to provide a comprehensive measure of whole-body tumor burden in patients with metastatic prostate cancer, and to standardize the evaluation of treatment-related changes. Therefore, we evaluated whether prostate-specific membrane antigen (PSMA) ligand PET/CT may be applied to provide PSMA-derived volumetric parameters for quantification of whole-body tumor burden. Methods: One hundred one patients who underwent 68Ga-PSMA I&T PET/CT because of increasing prostate-specific antigen (PSA) levels after radical prostatectomy were included in this retrospective analysis. Tracer uptake was quantified using SUVs. Volumetric parameters, that is, PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA (TL-PSMA), were calculated for each patient using a 3-dimensional segmentation and computerized volumetry technique and compared with serum PSA levels. In a group of 10 patients, volumetric parameters were applied for treatment monitoring. Results: Volumetric parameters, that is, whole-body PSMA-TV and whole-body TL-PSMA, demonstrated a statistically significant correlation with PSA levels (P < 0.0001) as a surrogate marker of tumor burden, whereas SUVmax (P = 0.22) or SUVmean (P = 0.45) did not. Treatment response and treatment failure were paralleled by concordant changes in both whole-body PSMA-TV and whole-body TL-PSMA (P = 0.02), whereas neither the change in SUVmax (P = 1.0) nor the change in SUVmean (P = 1.0) concordantly paralleled changes in PSA levels. Conclusion: PSMA-derived volumetric parameters provide a quantitative imaging biomarker for whole-body tumor burden, capable of standardizing quantitative changes in PET imaging of patients with metastatic prostate cancer and of facilitating therapy monitoring.

Incidental findings in cardiac magnetic resonance imaging: superiority of bSSFP over T1w-HASTE for extra-cardiac findings assessment.

Incidental findings are frequent in radiological examinations and may have an impact on further patient management. The aim of this retrospective study was to analyze, which of two thoracic scout sequences is more suitable for detecting incidental extra-cardiac findings at cardiac magnetic resonance imaging (CMRI) with stress perfusion. During a 14-month period clinically indicated stress perfusion CMRI was performed in 97 consecutive patients. For anatomical orientation ECG-triggered (electrocardiography) T1w-Half-fourier acquisition single-shot turbo spin-echo (HASTE) and balanced steady state free precession (bSSFP) sequences were performed for planning the standard cardiac sequences. Two radiologists independently studied incidental extra-cardiac findings with both sequences and rated the diagnostic confidence of the sequences for this assessment using a multinomial model. Furthermore, the interobserver agreement between the observers was assessed by weighted kappa statistics. Eight patients without incidental findings were excluded. In the other 89 patients a total of 153 incidental extra-cardiac findings were observed. Overall, 47.1% of findings were seen with better diagnostic confidence at bSSFP as opposed to 20.6% at T1w-HASTE. 32.4% of findings were equally well seen with both sequences. Consequently the bSSFP sequence was significantly better in terms of diagnostic confidence for detecting the majority of extra-cardiac incidental findings (P < 0.01), whereas a minority of findings was better visible by the HASTE sequence. The weighted kappa statistics was 0.85, indicating good interobserver agreement. Compared with T1w-HASTE, the bSSFP sequence improved the visibility of incidental extra-cardiac findings at stress perfusion CMRI. While all findings were seen on both sequences, bSSFP resulted in improved diagnostic confidence, and the T1w-HASTE sequence provided complementary diagnostic information in only a minority of patients.

Comparison of standard and delayed imaging to improve the detection rate of [68Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer.

PURPOSE: The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [68Ga]PSMA I&T. METHODS: 240 patients who underwent a [68Ga]PSMA I&T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging. RESULTS: The overall detection rates of [68Ga]PSMA I&T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P < 0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [68Ga]PSMA I&T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease. CONCLUSIONS: [68Ga]PSMA I&T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study.

Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging.

PURPOSE: The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point Ga-prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. METHODS: Twenty patients with prostate cancer underwent Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. RESULTS: Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ≤ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). CONCLUSIONS: Primary prostate cancer is readily identified on early dynamic and static delayed Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.