Is there more than meets the eye in PSMA imaging in prostate cancer with PET/MRI? Looking closer at uptake time, correlation with PSA and Gleason score.

BACKGROUND: In patients with increasing PSA and suspicion for prostate cancer, but previous negative biopsies, PET/MRI is used to test for tumours and target potential following biopsy. We aimed to determine different PSMA PET timing effects on signal kinetics and test its correlation with the patients' PSA and Gleason scores (GS). METHODS: A total of 100 patients were examined for 900 s using PET/MRI approximately 1-2 h p.i. depending on the tracer used (68Ga-PSMA-11, 18F-PSMA-1007 or 18F-rhPSMA7). The scans were reconstructed in static and dynamic mode (6 equal frames capturing "late" PSMA dynamics). TACs were computed for detected lesions as well as linear regression plots against time for static (SUV) and dynamic (SUV, SUL, and percent injected dose per gram) parameters. All computed trends were tested for correlation with PSA and GS. RESULTS: Static and dynamic scans allowed unchanged lesion detection despite the difference in statistics. For all tracers, the lesions in the pelvic lymph nodes and bones had a mostly negative activity concentration trend (78% and 68%, resp.), while a mostly positive, stronger trend was found for the lesions in the prostate and prostatic fossa following RPE (84% and 83%, resp.). In case of 68Ga-PSMA-11, a strong negative (Rmin = - 0.62, Rmax = - 0.73) correlation was found between the dynamic parameters and the PSA. 18F-PSMA-1007 dynamic data showed no correlation with PSA, while for 18F-rhPSMA7 dynamic data, it was consistently low positive (Rmin = 0.29, Rmax = 0.33). All tracers showed only moderate correlation against GS (Rmin = 0.41, Rmax = 0.48). The static parameters showed weak correlation with PSA (Rmin = 0.24, Rmax = 0.36) and no correlation with GS. CONCLUSION: "Late" dynamic PSMA data provided additional insight into the PSMA kinetics. While a stable moderate correlation was found between the PSMA kinetics in pelvic lesions and GS, a significantly variable correlation with the PSA values was shown depending on the radiotracer used, the highest being consistently for 68Ga-PSMA-11. We reason that with such late dynamics, the PSMA kinetics are relatively stable and imaging could even take place at earlier time points as is now in the clinical routine.

PET/MR Technology: Advancement and Challenges.

When this article was written, it coincided with the 11th anniversary of the installation of our PET/MR device in Munich. In fact, this was the first fully integrated device to be in clinical use. During this time, we have observed many interesting behaviors, to put it kindly. However, it is more critical that in this process, our understanding of the system also improved - including the advantages and limitations from a technical, logistical, and medical perspective. The last decade of PET/MRI research has certainly been characterized by most sites looking for a "key application." There were many ideas in this context and before and after the devices became available, some of which were based on the earlier work with integrating data from single devices. These involved validating classical PET methods with MRI (eg, perfusion or oncology diagnostics). More important, however, were the scenarios where intermodal synergies could be expected. In this review, we look back on this decade-long journey, at the challenges overcome and those still to come.

Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

BACKGROUND: The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. METHODS AND RESULTS: We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and (18)F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). (18)F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). CONCLUSIONS: In this study, the intensity of (18)F-FDG uptake in the myocardium after acute myocardial infarction correlated inversely with functional outcome at 6 months. Thus, (18)F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury.

Multiparametric MR and PET Imaging of Intratumoral Biological Heterogeneity in Patients with Metastatic Lung Cancer Using Voxel-by-Voxel Analysis.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (DW-MRI) and imaging of glucose metabolism by positron emission tomography (FDG-PET) provide quantitative information on tissue characteristics. Combining the two methods might provide novel insights into tumor heterogeneity and biology. Here, we present a solution to analyze and visualize the relationship between the apparent diffusion coefficient (ADC) and glucose metabolism on a spatially resolved voxel-by-voxel basis using dedicated quantitative software. MATERIALS AND METHODS: In 12 patients with non small cell lung cancer (NSCLC), the primary tumor or metastases were examined with DW-MRI and PET using 18F-fluorodeoxyglucose (FDG). The ADC's from DW-MRI were correlated with standardized-uptake-values on a voxel-by-voxel basis using custom made software (Anima M3P). For cluster analysis, we used prospectively defined thresholds for 18F-FDG and ADC to define tumor areas of different biological activity. RESULTS: Combined analysis and visualization of ADC maps and PET data was feasible in all patients. Spatial analysis showed relatively homogeneous ADC values over the entire tumor area, whereas FDG showed a decreasing uptake towards the tumor center. As expected, restricted water diffusivity was notable in areas with high glucose metabolism but was also found in areas with lower glucose metabolism. In detail, 72% of all voxels showed low ADC values (<1.5x10(-3) mm2/s) and high tracer uptake of 18F-FDG (SUV>3.6). However, 83% of the voxels with low FDG uptake also showed low ADC values, increasingly towards the tumor center. CONCLUSIONS: Multiparametric analysis and visualization of DW-MRI and FDG-PET is feasible on a spatially resolved voxel-by-voxel respectively cluster basis using dedicated imaging software. Our preliminary data suggest that water diffusivity and glucose metabolism in metastatic NSCLC are not necessarily correlated in all tumor areas.

PET/MRI early after myocardial infarction: evaluation of viability with late gadolinium enhancement transmurality vs. 18F-FDG uptake.

AIMS: F-18 fluorodeoxyglucose (FDG) myocardial PET imaging is since more than two decades considered to delineate glucose utilization in dysfunctional but viable cardiomyocytes. Late gadolinium enhancement (LGE) MRI was introduced more than a decade ago and identifies increased extravascular space in areas of infarction and scar. Although the physiological foundation differs, both approaches are valuable in the prediction of functional outcome of the left ventricle, but synergistic effects are yet unknown. We aimed to compare the improvement of LV function after 6 months based on the regional FDG uptake and the transmurality of scar by LGE in patients early after acute myocardial infarction (AMI). METHODS AND RESULTS: Twenty-eight patients with primary AMI underwent simultaneous PET/MRI for assessment of regional FDG uptake and degree of LGE transmurality 5-7 days after PCI. Follow-up by MRI was performed in 20 patients 6 months later. Myocardium was defined 'PET viable' based on the established threshold of ≥ 50% FDG uptake compared with remote myocardium or as 'MRI viable' when LGE transmurality of ≤ 50% was present. Regional wall motion was measured by MRI. Ninety-five dysfunctional segments were further analysed regarding regional wall motion recovery. There was a substantial intermethod agreement for segmental LGE transmurality and reduction of FDG uptake (κ = 0.65). 'PET viable' and 'MRI viable' segments showed a lower wall motion abnormality score (PET: initial: 1.4 ± 0.6 vs. 1.9 ± 0.8, P < 0.008; follow-up: 0.5 ± 0.7 vs. 1.5 ± 1.0, P < 0.0001; MRI: initial: 1.5 ± 0.6 vs. 2.0 ± 0.8, P < 0.002; follow-up: 0.7 ± 0.8 vs. 1.6 ± 1.0, P < 0.0001) and a better regional wall motion improvement (PET: -0.9 ± 0.7 vs. -0.4 ± 0.7, P < 0.0007; MRI: -0.8 ± 0.7 vs. -0.4 ± 0.7, P < 0.009) compared with 'PET non-viable' or 'MRI non-viable' segments, respectively. Eighteen per cent of the dysfunctional segments showed discrepant findings ('PET non-viable' but 'MRI viable'). At follow-up, the regional wall motion of these segments was inferior compared with 'PET viable/MRI viable' segments (1.1 ± 0.8 vs. 0.5 ± 0.7, P < 0.01), had an inferior functional recovery (-0.5 ± 0.6 vs. -0.9 ± 0.7, P < 0.03), but showed no difference compared with concordant 'PET non-viable/MRI non-viable' segments. CONCLUSION: The simultaneous assessment of LGE and FDG uptake using a hybrid PET/MRI system is feasible. The established PET and MRI 'viability' parameter prior to revascularization therapy also predicts accurately the regional outcome of wall motion after AMI. In a small proportion of segments with discrepant FDG PET and LGE MRI findings, FDG uptake was a better predictor for functional recovery.

Quantitative assessment of glucose metabolism in the vessel wall of abdominal aortic aneurysms: correlation with histology and role of partial volume correction.

Inflammatory-proteolytic processes in the vessel wall are essential in the pathophysiology of abdominal aortic aneurysm (AAA). It has been demonstrated that, (18)F-FDG-PET/CT may be useful for detection of pathological wall metabolism and therefore risk stratification. Quantification of the FDG-uptake in AAA wall is hampered by partial-volume (PV)-effects. For correction and accurate quantitative (18)F-FDG-uptake analysis we designed and validated a novel IDL-based software in correlation to phantom studies, histopathology and clinical presentation of AAA patients. For in vivo studies 23 patients with symptomatic and asymptomatic AAA underwent (18)F-FDG-PET/CT before surgery. In areas with (18)F-FDG-uptake the maximum and mean standardized uptake values in the vessel wall with (PVC-SUV(max), PVC-SUV(mean)) and without (SUV(max), SUV(mean)) PV-correction were determined. Results were correlated with clinical presentation, corresponding macrophage-infiltration and MMP-2- and -9-expression in surgical specimens. In patients, SUV(max), SUV(mean) as well as PVC-SUV(max) or PVC-SUV(mean) enabled a highly significant (p < 0.005) discrimination of symptomatic and asymptomatic AAA. Uncorrected and corrected SUVs showed comparable correlations with macrophage-infiltration and MMP-9 expression. No correlation of (18)F-FDG-uptake and MMP-2 was found. In vivo correlations of detected FDG-uptake with clinical and histological results showed comparable results for corrected and uncorrected SUVs. PV-correction is not mandatory for qualitative clinical assessment of glucose metabolism in the vessel wall of AAA-patients but may be necessary to establish quantitative cut off values to stratify patients for aneurysm repair.

Phenotyping of tumor biology in patients by multimodality multiparametric imaging: relationship of microcirculation, alphavbeta3 expression, and glucose metabolism.

UNLABELLED: Both dynamic contrast-enhanced (DCE) MRI and PET provide quantitative information on tumor biology in living organisms. However, imaging biomarkers often neglect tissue heterogeneity by focusing on distributional summary statistics. We analyzed the spatial relationship of α(v)ß(3) expression, glucose metabolism, and perfusion by PET and DCE MRI, focusing on tumor heterogeneity. METHODS: Thirteen patients with primary or metastasized cancer (non-small cell lung cancer, n = 9; others, n = 4) were examined with DCE MRI and with PET using (18)F-galacto-RGD and (18)F-FDG. Twenty-three different regions of interest were defined by cluster analysis based on the heterogeneity of tracer uptake. In these regions, the initial area under the gadopentetate dimeglumine concentration-time curve (IAUGC), as well as the regional blood volume (rBV) and regional blood flow (rBF), were estimated from DCE MRI and correlated with standardized uptake values from PET. RESULTS: Regions with simultaneously high uptake of (18)F-galacto-RGD and (18)F-FDG showed higher functional MRI data (IAUGC, 0.35 ± 0.04 mM·s; rBF, 70.2 ± 12.7 mL/min/100 g; rBV, 23.3 ± 2.7 mL/100 g) than did areas with low uptake of both tracers (IAUGC, 0.15 ± 0.04 mM·s [P < 0.01]; rBF, 28.3 ± 10.8 mL/min/100 g; rBV, 9.9 ± 1.9 mL/100 g [P < 0.01]). There was a weak to moderate correlation between the functional MRI parameters and (18)F-galacto-RGD (r = 0.30-0.62) and also (18)F-FDG (r = 0.44-0.52); these correlations were significant (P < 0.05), except for (18)F-galacto-RGD versus rBF (P = 0.17). CONCLUSION: These data show that multiparametric assessment of tumor heterogeneity is feasible by combining PET and MRI. Perfusion is highest in tumor areas with simultaneously high α(v)ß(3) expression and high glucose metabolism and restricted in areas with both low α(v)ß(3) expression and low glucose metabolism. The current limitations resulting from imaging with separate scanners might be overcome by future hybrid PET/MRI scanners.