Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

Patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer.

BACKGROUND: Sentinel lymph node mapping is a minimally invasive surgical staging procedure that allows identification of macro- and micrometastases. The implementation of sentinel lymph node mapping to women with low-grade endometrial cancer allows detection of lymph node metastases and avoids the morbidity of radical pelvic lymphadenectomy. The extent of myometrial invasion is highly predictive of lymph node metastases but is hard to determine precisely preoperatively. The exact rate of lymph node metastases in the large group of women with <50% myometrial invasion is low but unknown. The benefit of detecting metastases in this group should balance the risk of lymphedema. There is limited knowledge of early and late lymphedema and its impact on the quality of life in women with low-grade endometrial cancer following sentinel lymph node mapping. OBJECTIVE: The primary objective was to investigate the risk of patient-reported lymphedema after SLN mapping in women with low-grade endometrial cancer. In addition, we aimed to evaluate risk factors for lymphedema and the condition-specific quality of life (QoL) among women who reported lymphedema 12 months after surgery. STUDY DESIGN: Women with presumed stage I low-grade endometrial cancer were included in a national prospective cohort study on SLN mapping from March 2017-February 2022. Women completed a package of validated patient-reported outcome measures (PROMs) before surgery, three and 12 months after surgery. The primary outcome was the leg lymphedema domain score from the European Organisation for Research and Treatment of Cancer endometrial cancer-specific module (EORTC QLQ-EN24). The lymphedema assessment was further supplemented by seven validated single items from the EORTC item library addressing lymphedema of legs, genitals, and groin. The disease-specific QoL was assessed using the validated Lymphedema quality of life tool (LYMQOL). Scores were linearly transformed to 0-100. A change from baseline of 8 points in leg lymphedema sum-score was considered clinically important. Mean difference scores over time with 95% CI were estimated. Multiple linear regression models evaluated baseline predictors associated with the 12 month postoperative lymphedema score, and if early lymphedema predicted lymphedema at 12 months after surgery. Lymphedema condition-specific QoL was evaluated for women with lymphedema. RESULTS: Seventy-nine % (486/617) completed PROMs at baseline and 12 months. The mean difference score of leg lymphedema from baseline to 12 months was 5.0, CI [3.3, 6.8], i.e., below the threshold for clinical importance. Baseline leg lymphedema score and BMI were positively associated with the leg lymphedema score at 12 months. The leg lymphedema score at three months was associated with a higher 12-month score. High scores of lymphedema at 12 months were negatively associated with the women's daily activities, appearance, emotional functioning, and global QoL and increased their subjective symptom burden. CONCLUSIONS: Women with low-grade endometrial cancer have a low risk of lymphedema after SLN mapping. Leg swelling at baseline and BMI predicted more lymphedema at 12 months after surgery. Early lymphedema at three months predicted persistent lymphedema. A high leg lymphedema score at 12 months is associated with impairment in several aspects of QoL.

Quantitative and qualitative comparison of Rubidium-82 and Oxygen-15 water cardiac PET.

BACKGROUND: Differences in tracer characteristics may influence the interpretation of positron emission tomography myocardial perfusion imaging (MPI). We compare the reading of MPIs with a low-extraction retention tracer (82Rb) and a high-extraction non-retention tracer (15O-water) in a selected cohort of patients with known coronary artery disease (CAD). METHODS: Thirty-nine patients with known CAD referred to 82Rb MPI due to angina underwent rest and stress imaging with both tracers and experienced MPI readers provided blinded consensus reads of all studies. In addition, a comparison of regional and global quantitative measures of perfusion was performed. RESULTS: The results showed 74 % agreement in the reading of 82Rb and 15O-water MPI for regional reversible ischemia and global disease, and 82 % agreement for regional irreversible ischemia. The 15O-water MPI identified more cases of global disease (n = 12 (15O-water) vs n = 4 (82Rb), p = 0.03), whereas differences in reversible ischemia (n = 22 vs n = 16, p = 0.11) and, irreversible ischemia (n = 8 vs n = 11, p = 0.45) were not significant. The correlation between myocardial blood flow measured using the two tracers was similar to previous studies (R2 = 0.78) with wide limits of agreement (-0.93 to 0.84 ml/g/min). CONCLUSIONS: Agreement between consensus readings of 82Rb and 15O-water MPI was good in patients with known CAD. In this limited size study, no significant differences in the identification of reversible and irreversible ischemia found, whereas 15O-water MPI had a higher positive rate for suspected global disease.

The diagnostic accuracy of radiolabeled PSMA-ligand PET for tumour staging in newly diagnosed prostate cancer patients compared to histopathology: a systematic review and meta-analysis.

PURPOSE: The current clinical recommendations posit the deployment of specific approved radiolabeled prostate-specific membrane antigen-ligand positron emission tomography (PSMA PET) for detecting metastatic prostate cancer during primary staging. Nevertheless, the precise efficacy of such ligands in localizing intraprostatic tumours (index tumour) and T-staging is not well established. Consequently, the objective of this inquiry is to ascertain the diagnostic accuracy of PSMA-PET in the tumour staging of newly diagnosed prostate cancer by means of a meta-analysis that integrates studies utilizing histological confirmation as the reference standard. METHODS: In this study, we conducted a systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases using a predefined collection of search terms. These terms included 'PSMA PET', 'primary staging', and 'prostate cancer'. Subsequently, two independent reviewers evaluated all the studies based on predetermined inclusion criteria, extracted pertinent data, and assessed the quality of evidence. Any disparities were resolved by a third reviewer. A random effects Sidik-Jonkman model was applied to conduct a meta-analysis and estimate the diagnostic accuracy on a per-patient basis, along with 95% confidence intervals. Moreover, an appraisal regarding the likelihood of publication bias and the impact of small-study effects was performed utilizing both Egger's test and a graphical examination of the funnel plot. RESULTS: The present analysis comprised a total of twenty-three scientific papers encompassing 969 patients and involved their analysis by both qualitative and quantitative approaches. The results of this study demonstrated that the estimated diagnostic accuracy of PSMA PET/CT and PSMA PET/MRI, for the detection of intraprostatic tumours, regardless of the type of PSMA-ligand, was 86% (95% CI: 76-96%) and 97% (95% CI: 94-100%), respectively. Furthermore, the diagnostic accuracy for the detection of extraprostatic extension (EPE) was 73% (95% CI: 64-82%) and 77% (95% CI: 69-85%), while the diagnostic accuracy for the detection of seminal vesicle involvement (SVI) was 87% (95% CI: 80-93) and 90% (95% CI: 82-99%), respectively. CONCLUSION: The present investigation has demonstrated that PSMA PET/MRI surpasses currently recommended multiparametric magnetic resonance imaging (mpMRI) in terms of diagnostic accuracy as inferred from a notable data trajectory, whereas PSMA-PET/CT exhibited comparable diagnostic accuracy for intraprostatic tumour detection and T-staging compared to mpMRI. Nevertheless, the analysis has identified certain potential limitations, such as small-study effects and a potential for publication bias, which may impact the overall conclusions drawn from this study.

The SENTIREC-endo study - Risks and benefits of a national adoption of sentinel node mapping in low and intermediate risk endometrial cancer.

OBJECTIVE: The SENTIREC-endo study aims to investigate risks and benefits of a national protocolled adoption of sentinel lymph node (SLN) mapping in women with early-stage low-grade endometrial cancer (EC) with low- (LR) and intermediate-risk (IR) of lymph node metastases. METHODS: We performed a national multicenter prospective study of SLN-mapping in women with LR and IR EC from March 2017-February 2022. Postoperative complications were classified according to Clavien-Dindo. Lymphedema was assessed as a change score and as incidence of swelling and heaviness evaluated by validated patient-reported outcome measures at baseline and three months postoperatively. RESULTS: 627 women were included in the analyses; 458 with LR- and 169 with IR EC. The SLN detection rate was 94.3% (591/627). The overall incidence of lymph node metastases was 9.3% (58/627); 4.4% (20/458) in the LR- and 22.5% (38/169) in the IR group. Ultrastaging identified 62% (36/58) of metastases. The incidence of postoperative complications was 8% (50/627) but only 0.3% (2/627) experienced an intraoperative complication associated with the SLN procedure. The lymphedema change score was below the threshold for clinical importance 4.5/100 CI: (2.9-6.0), and the incidence of swelling and heaviness was low; 5.2% and 5.8%, respectively. CONCLUSION: SLN mapping in women with LR and IR EC carries a very low risk of early lymphedema and peri- and postoperative complications. The national change in clinical practice contributed to a more correct treatment allocation for both risk groups and thus supports further international implementation of the SLN technique in early stage, low grade EC.

Activity regimes for 82Rb cardiac PET: Effects on absolute MBF and MPI.

BACKGROUND: Selection of optimal tracer activity for 82Rb PET is based on a trade-off between necessary count-statistics in the late static phase and detector saturation in the early blood-pool phase. Administered tracer activity recommended in prescribing information differs substantially from recommendations in current literature. The present study examines the effect on both absolute myocardial blood flow (MBF), myocardial flow reserve (MFR) and relative myocardial perfusion imaging (MPI) of reducing dose. METHODS: Forty patients were scanned twice on a PMT-based PET/CT (GE D690): At recommended activity (1110 MBq) and at either 740 or 370 MBq. MBF, MFR, total perfusion deficit (TPD) and ejection fractions (EF) were quantified. Results were compared using linear regression and Bland-Altman plots. RESULTS: Linear correlation between MBF at 1110 MBq at either reduced activity had an R2 > 0.98. A small bias (± 5%-9%) was observed with opposite signs for 1110/740 and 1110/370. Limits of agreement for MBF were larger for 1110/370. MFR had a lower linear correlation (R2 = 0.96), but wide limits of agreement especially for 1110/370. TPD and EF correlated well at 1110/740 (R2 = 0.96 and 0.99, respectively), but large scatter was observed for 1110/370. CONCLUSION: Reduction of the tracer activity to 740 MBq, significantly reduced dead-time correction factors, while still producing reliable static and gated images. However, despite large dead-time at 1110 MBq, no systematic bias on absolute MBF was observed compared to reduced activities.

Recurrence rate after radical prostatectomy following primary staging of high-risk prostate cancer with 68Ga-PSMA PET/CT.

BACKGROUND: Accurate primary staging is one of the most important issues for initial management of prostate cancer (PCa) patients to perform an optimal selection of patients for curative intended treatment. 68Ga-Prostate-Specific-Membrane-Antigen (PSMA) PET/CT was found superior to conventional imaging both for detection of recurrence after curative intended treatment and for primary staging. We studied the recurrence rate after radical prostatectomy in high-risk PCa patients primary staged with 68Ga-PSMA PET/CT compared with conventional imaging. MATERIAL AND METHODS: The study included 247 D'Amico high-risk PCa patients treated with radical prostatectomy (RP) after primary staging with 68Ga-PSMA PET/CT and a reference group of 137 high-risk patients with RP after conventional imaging (99mTc bone scintigraphy and CT). Recurrence rates were assessed by Cox regression and Kaplan-Meier analysis. RESULTS: The 5-year recurrence-free survival rate was 71.1% in the 68Ga-PSMA PET/CT cohort compared with 56.4% in the conventional imaging cohort. Primary staging by 68Ga-PSMA PET/CT reduced biochemical recurrence (BCR) risk by 42% (HR = 0.58 (0.41-0.83), p = .004). CONCLUSION: The present data could indicate a lower recurrence rate after RP following primary staging with 68Ga-PSMA PET/CT compared to conventional imaging, likely due to improved selection of patients for surgery.

Tumour blood flow for prediction of human prostate cancer aggressiveness: a study with Rubidium-82 PET, MRI and Na+/K+-ATPase-density.

PURPOSE: Tumour blood flow (TBF) is a crucial determinant of cancer growth. Recently, we validated Rubidium-82 (82Rb) positron emission tomography (PET) for TBF measurement in prostate cancer (PCa) and found TBF and cancer aggressiveness positively correlated. The aims of the present study were to determine the ability of TBF for separating significant from insignificant PCa and to examine the relation to underlying Na+/K+-ATPase density, which is relevant as 82Rb is transported intracellularly via the Na+/K+-ATPase. METHODS: One hundred and two patients were included for pelvic 82Rb PET scan prior to magnetic resonance imaging (MRI)-guided prostate biopsy. Findings constituted 100 PCa lesions (86 patients) and 25 benign lesions (16 patients). Tumours were defined on MRI and transferred to 82Rb PET for TBF measurement. Immunohistochemical Na+/K+-ATPase staining was subsequently performed on biopsies. RESULTS: TBF was the superior predictor (rho = 0.68, p < 0.0001, inflammatory lesions excluded) of MRI-guided biopsy grade group (GG) over lowest apparent diffusion coefficient (ADC) value (rho = -0.23, p = 0.01), independent of ADC value and tumour volume (p < 0.0001). PET could separate GG-2-5 from GG-1 and benign lesions with an area under the curve (AUC), sensitivity, and specificity of 0.79, 96%, and 59%, respectively. For separating GG-3-5 from GG-1-2 and benign lesions the AUC, sensitivity, and specificity were 0.82, 95%, and 63%, respectively. Na+/K+-ATPase density per PCa cell profile was 38% lower compared with that of the benign prostate cell profiles. Neither cell density nor Na+/K+-ATPase density determined tumour 82Rb uptake. CONCLUSION: TBF is an independent predictor of PCa aggressiveness and deserves more attention, as it may be valuable in separating clinically significant from insignificant PCa.

DaPeCa-7: comparative assessment of fluorodeoxyglucose positron emission tomography/computed tomography (CT) and conventional diagnostic CT in diagnosis of lymph node metastases, distant metastases and incidental findings in patients with invasive penile cancer.

OBJECTIVES: To evaluate diagnostic accuracy of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) compared to contrast-enhanced CT in assessment of inguinal lymph node (ILN) metastases, distant metastases and synchronous cancers in patients with penile squamous cell carcinoma (pSCC). PATIENTS AND METHODS: During a 4-year period, patients with pSCC were scheduled for FDG PET/CT prior to surgical treatment at two referral centres that manage all penile cancers in Denmark. The primary endpoint was diagnostic accuracy of FDG PET/CT and of CT alone with histopathology or Response Evaluation Criteria In Solid Tumors (RECIST) as reference. RESULTS: We evaluated 171 patients for distant metastases and synchronous incident cancers and examined 286 groins in 143 patients for LN metastases by FDG PET/CT. Six groins disclosed false negatives. FDG PET/CT sensitivity was 85.4% per patient. In 135 patients (270 groins), CT images were evaluated separately and 22 groins disclosed false negatives. CT sensitivity was 47.5% per patient. FDG PET/CT detected pSCC distant metastases in seven patients. Distant metastases from other cancers were newly detected in three patients. In eight patients, an incidental synchronous cancer was detected. Seven out of the 18 distant malignancies detected depended on FDG PET information. CONCLUSION: This study underlines the increased diagnostic accuracy of FDG PET/CT compared to CT alone in the evaluation of ILN status. In patients with palpable LNs, the advantage of FDG PET/CT over CT is less pronounced. FDG PET/CT may play a role in penile cancer evaluation.

Micro- and macrovascular cardiac allograft vasculopathy in relation to 91 cardiovascular biomarkers in heart transplant recipients-An exploratory study.

BACKGROUND: Cardiac allograft vasculopathy (CAV) limits survival after heart transplantation (HTx), and the pathogenesis is not fully clarified. We aimed to investigate a wide range of biomarkers and their correlation with micro- and macrovascular CAV and major adverse cardiac events in HTx patients. METHODS: We evaluated 91 cardiovascular disease-related proteins in 48 HTx patients using a novel proteomic panel. Patients were dichotomized according to micro- and macrovascular CAV burden determined by coronary angiography, optical coherence tomography, and 15 O-H2 O positron emission tomography imaging. Major adverse cardiac events included significant CAV progression, heart failure, treated rejection, and cardiovascular death. RESULTS: We found consistent differences in two proteins involved in cholesterol homeostasis: significantly increased proprotein convertase subtilisin/kexin type 9 (PCSK9) (p < .05) and significantly decreased paraoxonase 3 (PON3) (p < .05). N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly increased in patients with microvascular CAV (p < .05) and borderline significantly increased in patients experiencing major adverse cardiac events (p = .10) and patients with macrovascular CAV (p = .05). CONCLUSIONS: We identified consistent changes in two proteins involved in cholesterol homeostasis which may be important players in the pathogenesis of CAV: PON3 and PCSK9. NT-proBNP also showed consistent changes across all groups but only reached statistical significance in patients with microvascular CAV. Our results warrant further validation in future studies.

PET imaging in renal cancer.

PURPOSE OF REVIEW: Worldwide, over 400 000 new cases of kidney cancer were diagnosed and over 175 000 deaths anticipated in 2018. It is ranked as the 14th most common cancer in women and 9th most common in men. Imaging is important for initial detection, staging, and monitoring to assist treatment planning, but conventional anatomic imaging is limited. Although functional PET/CT has proven helpful in the diagnosis and management of many cancers, its value in renal cell carcinoma (RCC) is still in evolution. RECENT FINDINGS: FDG is probably the most useful radiotracer in RCC, although CAIX imaging can be helpful in clear cell RCC. Current research on PET imaging agents in RCC including 89Zr bevacizumab, 89Zr geruntuximab, 18F fluoro-L-thymidine (FLT), prostate-specific membrane antigen (PSMA), 11C choline, 18F sodium fluoride (NaF), and18F fluorodeoxyglucose (FDG) have shown some interesting results for detection and prognosis of the disease. SUMMARY: Many innovative radiotracers have been tested in RCC, but robust differentiation of primary disease from normal parenchyma remains elusive for almost all of them. The metastatic setting and response to therapy for this cancer are more favorable PET applications. Continued research in promising molecular tracers will hopefully advance both diagnostic and therapeutic strategies to ultimately eradicate RCC.

Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study.

BACKGROUND: The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). METHODS AND RESULTS: CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by 18F-FDG and 15O-H2O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide. CONCLUSION: Liraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR. TRIAL REGISTRATION: Trial registry: http://www.ClinicalTrials.org . Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1.

Electrically vs. imaging-guided left ventricular lead placement in cardiac resynchronization therapy: a randomized controlled trial.

AIMS: To test in a double-blinded, randomized trial whether the combination of electrically guided left ventricular (LV) lead placement and post-implant interventricular pacing delay (VVd) optimization results in superior increase in LV ejection fraction (LVEF) in cardiac resynchronization therapy (CRT) recipients. METHODS AND RESULTS: Stratified according to presence of ischaemic heart disease, 122 patients were randomized 1:1 to LV lead placement targeted towards the latest electrically activated segment identified by systematic mapping of the coronary sinus tributaries during CRT implantation combined with post-implant VVd optimization (intervention group) or imaging-guided LV lead implantation by cardiac computed tomography venography, 82Rubidium myocardial perfusion imaging and speckle tracking echocardiography targeting the LV lead towards the latest mechanically activated non-scarred myocardial segment (control group). Follow-up was 6 months. Primary endpoint was absolute increase in LVEF. Additional outcome measures were changes in New York Heart Association class, 6-minute walk test, and quality of life, LV reverse remodelling, and device related complications. Analysis was intention-to-treat. A larger increase in LVEF was observed in the intervention group (11 ± 10 vs. 7 ± 11%; 95% confidence interval 0.4-7.9%, P = 0.03); when adjusting for pre-specified baseline covariates this difference did not maintain statistical significance (P = 0.09). Clinical response, LV reverse remodelling, and complication rates did not differ between treatment groups. CONCLUSION: Electrically guided CRT implantation appeared non-inferior to an imaging-guided strategy considering the outcomes of change in LVEF, LV reverse remodelling and clinical response. Larger long-term studies are warranted to investigate the effect of an electrically guided CRT strategy.

Transmural Myocardial Scar Assessed by Cardiac Computed Tomography: Predictor of Echocardiographic Versus Clinical Response to Cardiac Resynchronization Therapy?

OBJECTIVES: Before cardiac resynchronization therapy (CRT) implantation, cardiac computed tomography (CT) can provide assessment of cardiac venous anatomy and visualize left ventricular (LV) myocardial scar. We hypothesized that localization and burden of transmural myocardial scar verified by cardiac CT are associated with echocardiographic and clinical response to CRT. METHODS: We prospectively included 140 CRT recipients undergoing preimplant cardiac CT. We assessed transmural scar, defined as hypoperfusion involving more than one-half of the myocardial wall in each LV segment using a 17-segment model. Echocardiographic nonresponse was defined as less than 5% absolute improvement in LV ejection fraction at 6 months' follow-up. Clinical nonresponse was defined as 1 or more of the following at 6 months' follow-up: death, heart failure hospitalization, or no improvement in New York Heart Association class and less than 10% increase in 6-minute walk-test distance. RESULTS: Higher burden of myocardial scar was associated with echocardiographic nonresponse (adjusted odds ratio, 3.02; 95% confidence interval, 1.03-8.91; P = 0.045). Scar concordant or adjacent to LV pacing site was associated with echocardiographic nonresponse (adjusted odds ratio, 8.2; 95% confidence interval, 1.51-44.27; P = 0.015). No association between scar and clinical nonresponse was demonstrated. CONCLUSIONS: Higher scar burden and scar in proximity to the LV pacing site assessed by cardiac CT are associated with echocardiographic nonresponse to CRT. Burden and location of scar were not associated with clinical nonresponse. Further large-scale studies are needed to assess the potential association between myocardial scar detected by cardiac CT and clinical CRT outcome.

Advances in prostate-specific membrane antigen PET of prostate cancer.

PURPOSE OF REVIEW: In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. RECENT FINDINGS: PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. SUMMARY: Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

Effect of remote ischemic conditioning on myocardial perfusion in patients with suspected ischemic coronary artery disease.

BACKGROUND: Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury and may modulate coronary blood flow. We investigated whether RIC affects resting myocardial perfusion (MP) in patients with suspected ischemic coronary artery disease by quantitative MP imaging. METHODS AND RESULTS: We included 49 patients with suspected ischemic coronary artery disease. Resting MP was quantified by 82Rubidium positron emission tomography/computed tomography (82Rb-PET/CT) imaging before and after RIC, performed as four cycles of 5 minutes upper arm ischemia and reperfusion. Subsequent adenosine 82Rb-PET/CT stress-imaging identified non-ischemic and reversibly ischemic myocardial segments. MicroRNA-144 plasma levels were measured before and after RIC. Normalized for rate pressure product, RIC did not affect MP globally (P = .64) or in non-ischemic myocardial segments (P = .58) but decreased MP in reversibly ischemic myocardial segments (-0.11 mL/min/g decrease in MP following RIC; 95% CI -0.17 to -0.06, P < .001). However, we found no effect of RIC when MP was normalized for cardiac work. MicroRNA-144 plasma levels increased following RIC (P = .006) but did not correlate with a change in global MP in response to RIC (P = .40). CONCLUSIONS: RIC did not substantially affect resting MP globally or in non-ischemic and reversibly ischemic myocardial territories in patients with suspected ischemic coronary artery disease.

Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism.

BACKGROUND: In type 2 diabetes, a decrease in myocardial glucose uptake (MGU) may lower glucose oxidation and contribute to progression of chronic heart failure (CHF). However, it is unsettled whether CHF patients with prediabetes have abnormal MGU and myocardial blood flow (MBF) during normal physiological conditions. METHODS AND RESULTS: We studied 35 patients with CHF and reduced left ventricular ejections fraction (34 ± 9%) without overt T2D (mean HbA1c: 40 ± 4 mmol/mol) using echocardiography and quantitative measurements of MGU by 18F-FDG-PET and perfusion by 15O-H2O-PET. An oral glucose tolerance test (OGTT) was performed during the FDG-PET, which identified 17 patients with abnormal and 18 patients with normal glucometabolic response. Global MGU was higher in patients with normal OGTT response (0.31 ± 0.09 µmol/g/min) compared with patients with abnormal OGTT response (0.25 ± 0.09 µmol/g/min) (P = 0.05). MBF (P = 0.22) and myocardial flow reserve (MFR) (P = 0.83) were similar in the study groups. The reduced MGU in prediabetic patients was attributable to reduced MGU in viable myocardium with normal MFR (P < 0.001). CONCLUSION: CHF patients with prediabetes have reduced MGU in segments with preserved MFR as compared to CHF patients with normal glucose tolerance. Whether reversal of these myocardial abnormalities can improve outcome needs to be investigated in large-scale studies.

Test-retest repeatability of myocardial oxidative metabolism and efficiency using standalone dynamic 11C-acetate PET and multimodality approaches in healthy controls.

BACKGROUND: Myocardial efficiency measured by 11C-acetate positron emission tomography (PET) has successfully been used in clinical research to quantify mechanoenergetic coupling. The objective of this study was to establish the repeatability of myocardial external efficiency (MEE) and work metabolic index (WMI) by non-invasive concepts. METHODS AND RESULTS: Ten healthy volunteers (63 ± 4 years) were examined twice, one week apart, using 11C-acetate PET, cardiovascular magnetic resonance (CMR), and echocardiography. Myocardial oxygen consumption from PET was combined with stroke work data from CMR, echocardiography, or PET to obtain MEE and WMI for each modality. Repeatability was estimated as the coefficient of variation (CV) between test and retest. MEECMR, MEEEcho, and MEEPET values were 21.9 ± 2.7%, 16.4 ± 3.7%, and 23.8 ± 4.9%, respectively, P < .001. WMICMR, WMIEcho, and WMIPET values were 4.42 ± 0.90, 4.07 ± 0.63, and 4.58 ± 1.13 mmHg × mL/m2 × 106, respectively, P = .45. Repeatability for MEECMR was superior compared with MEEEcho but did not differ significantly compared with MEEPET (6.3% vs 12.9% and 9.4%, P = .04 and .25). CV values for WMICMR, WMIEcho, and WMIPET were 10.0%, 14.8%, and 12.0%, respectively, (P = .53). CONCLUSIONS: Non-invasive measurements of MEE using 11C-acetate PET are highly repeatable. A PET-only approach did not differ significantly from CMR/PET and might facilitate further clinical research due to lower costs and broader applicability.

Prostate-specific membrane antigen positron emission tomography in prostate cancer: a step toward personalized medicine.

PURPOSE OF REVIEW: Increasing attention is being given to personalized medicine in oncology, where therapies are tailored to the particular characteristics of the individual cancer patient. In recent years, there has been greater focus on prostate-specific membrane antigen (PSMA) in prostate cancer (PCa) as a target for imaging and therapy with radionuclides. This review highlights the recent advancements in PSMA positron emission tomography (PET) in PCa during the past year. RECENT FINDINGS: Several reports on PSMA PET/computed tomography (CT) in PCa patients are demonstrating promising results, especially for detection of biochemical recurrence. F-PSMA PET/CT may be superior to Ga-PSMA PET/CT. The detection rate of PSMA PET is influenced by prostate-specific antigen level. PSMA PET/CT may have a higher detection rate than choline PET/CT. Only a few reports have been published on PSMA PET/magnetic resonance imaging (MRI), and this modality remains to be elucidated further. SUMMARY: Molecular imaging with PSMA PET is paving the way for personalized medicine in PCa. However, large prospective clinical studies are needed to further evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa. PSMA is an excellent target for imaging and therapy with radionuclides, and the 'image and treat' strategy has the potential to become a milestone in the management of PCa patients.