Differences in cause and 12-month follow-up outcome of parkinsonian symptoms in depressed older adults treated with antipsychotics: a case series.

BACKGROUND: Parkinsonian symptoms are common adverse effects of antipsychotics. Older adults are particularly vulnerable to drug-induced parkinsonism. Nonetheless, parkinsonian symptoms in seniors treated with antipsychotics cannot be straightforwardly attributed to antipsychotic medication. A comprehensive diagnostic workup is necessary in many cases in order to shed light on the cause of such symptoms in this patient population. CASE SERIES: Eight cases of hospitalized depressed older adults with parkinsonian symptoms, who were treated for at least one year with antipsychotics, are reported. Based on neurological consultation, structural brain imaging and Ioflupane (I-123) dopamine transporter (DAT) single photon emission computerized tomography (SPECT), Parkinson's disease was diagnosed in one case, idiopathic tremor in another, vascular parkinsonism in another one, while in another individual parkinsonian symptoms persisted at 12-month post-discharge follow-up even though his/her symptoms were classified as drug-induced on discharge. In four patients, parkinsonian symptoms were definitely drug-induced and no movement disturbances were reported at follow-up. CONCLUSIONS: Differences in the cause and outcome of parkinsonian symptoms in seniors treated with antipsychotics merit systematic and in-depth study considering the therapeutic and prognostic implications of an accurate detection of the cause of such symptoms. Familiarizing clinical psychiatrists with these differences could pave the way towards approaching seniors with severe, atypical and/or persistent parkinsonian symptoms in a more individualized diagnostic and therapeutic manner, and towards more cautious prescribing of antipsychotics in this age group.

Prospective head-to-head comparison of 11C-choline-PET/MR and 11C-choline-PET/CT for restaging of biochemical recurrent prostate cancer.

PURPOSE: Whole-body integrated 11C-choline PET/MR might provide advantages compared to 11C-choline PET/CT for restaging of prostate cancer (PC) due to the high soft-tissue contrast and the use of multiparametric MRI, especially for detection of local recurrence and bone metastases. MATERIALS AND METHODS: Ninety-four patients with recurrent PC underwent a single-injection/dual-imaging protocol with contrast-enhanced PET/CT followed by fully diagnostic PET/MR. Imaging datasets were read separately by two reader teams (team 1 and 2) assessing the presence of local recurrence, lymph node and bone metastases in predefined regions using a five-point scale. Detection rates were calculated. The diagnostic performance of PET/CT vs. PET/MR was compared using ROC analysis. Inter-observer and inter-modality variability, radiation exposure, and mean imaging time were evaluated. Clinical follow-up, imaging, and/or histopathology served as standard of reference (SOR). RESULTS: Seventy-five patients qualified for the final image analysis. A total of 188 regions were regarded as positive: local recurrence in 37 patients, 87 regions with lymph node metastases, and 64 regions with bone metastases. Mean detection rate between both readers teams for PET/MR was 84.7% compared to 77.3% for PET/CT (p > 0.05). Local recurrence was identified significantly more often in PET/MR compared to PET/CT by team 1. Lymph node and bone metastases were identified significantly more often in PET/CT compared to PET/MR by both teams. However, this difference was not present in the subgroup of patients with PSA values ≤2 ng/ml. Inter-modality and inter-observer agreement (K > 0.6) was moderate to substantial for nearly all categories. Mean reduction of radiation exposure for PET/MR compared to PET/CT was 79.7% (range, 72.6-86.2%). Mean imaging time for PET/CT was substantially lower (18.4 ± 0.7 min) compared to PET/MR (50.4 ± 7.9 min). CONCLUSIONS: 11C-choline PET/MR is a robust imaging modality for restaging biochemical recurrent PC and interpretations between different readers are consistent. It provides a higher diagnostic value for detecting local recurrence compared to PET/CT with the advantage of substantial dose reduction. Drawbacks of PET/MR are a substantially longer imaging time and a slight inferiority in detecting bone and lymph node metastases in patients with PSA values >2 ng/ml. Thus, we suggest the use of 11C-choline PET/MR especially for patients with low (≤2 ng/ml) PSA values, whereas PET/CT is preferable in the subgroup with higher PSA values.

[11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy.

PURPOSE: Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. RESULTS: In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). METHODS: 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. CONCLUSIONS: The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

Intrapatient Comparison of 111In-PSMA I&T SPECT/CT and Hybrid 68Ga-HBED-CC PSMA PET in Patients With Early Recurrent Prostate Cancer.

PURPOSE: The aim of this study was to evaluate the detection efficiency of In-PSMA-I&T SPECT/CT in comparison to hybrid Ga-PSMA HBED-CC PET in patients with early recurrent prostate cancer. METHODS: Twenty-two patients (mean age, 68.2 ± 6.8 years; range, 52-76 years) with rising prostate-specific antigen (PSA; median, 1.03 ng/mL; range, 0.2-7.2ng/mL) and known positive lesions in hybrid Ga-PSMA HBED-CC PET scheduled for salvage surgery were included. Whole-body scintigraphy and SPECT/CT were performed 4 hours after application of 147.0 ± 24.8 MBq (range, 90-183 MBq) In-PSMA I&T. Images were evaluated for suspected lesions, and conspicuity of all lesions was rated using a 4-point-scale (0 = not seen, 1 = retrospectively seen in knowledge of Ga-PSMA HBED-CC PET, 2 = low signal, 3 = high signal). Tumor-to-background ratios were determined for SPECT and PET and compared. Tumor-to-background ratio of SPECT was correlated with lesion size as well as patients' Gleason score and PSA level. RESULTS: In-PSMA I&T SPECT/CT detected 14 of 29 PET-positive lesions (48.3%) with no additional lesions identified with In-PSMA I&T SPECT/CT. There was a significant weak to moderate correlation of PSA level with tumor-to-background ratio of In-PSMA I&T SPECT/CT (correlation coefficient r = 0.6406; 95% confidence interval, 0.1667-0.8741; P = 0.0136). There was no significant difference (P > 0.05), but a weak trend toward a higher detectability in In-PSMA I&T SPECT/CT regarding lesion size and initial PSA level. CONCLUSIONS: In a preselected collective of recurrent prostate cancer patients with low PSA values, In-PSMA I&T SPECT/CT showed lower detection rates than hybrid Ga-HBED-CC PSMA PET. However, In-PSMA I&T SPECT/CT showed a patient based detection rate of 59%, making it a potentially valuable imaging tool where PET is not available apart from its proven value as a PSMA-targeted probe for radioguided surgery.

Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET.

PURPOSE: Due to the high expression of the integrin αvß3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvß3-targeted tracers seems promising. However, little is known about the patterns of αvß3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvß3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. RESULTS: [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/-0.94 (range 0.70-4.38; tumor/blood 1.36+/-0.53; tumor/muscle 2.82+/-1.31) in bone-lesions and 2.21+/-1.18 (range 0.75-3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. METHODS: 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. CONCLUSIONS: Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvß3-targeted therapies due to the high variability of αvß3-expression.

Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer.

BACKGROUND: Ligands of the prostate-specific membrane antigen (PSMA) show promising results in positron emission tomography (PET) imaging of prostate cancer (PCa). OBJECTIVE: To compare the diagnostic performance of simultaneous gallium 68 (68Ga)-PSMA HBED-CC PET/magnetic resonance imaging (MRI) for localization of primary PCa with multiparametric magnetic resonance imaging (mpMRI) and PET alone. DESIGN, SETTING, AND PARTICIPANTS: We performed 68Ga-PSMA HBED-CC PET/MRI in 66 men with biopsy-proven PCa. INTERVENTION: PET, mpMRI, and combined 68Ga-PSMA HBED-CC PET/MRI were independently evaluated using Prostate Imaging Reporting and Data System criteria or a 5-point Likert scale. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The prostate was divided into sextants for histopathology and coregistered with imaging. Diagnostic performance for localization of malignancy was calculated based on receiver operating characteristics analysis for each modality. Regional quantitative PET tracer uptake was recorded; uptake ratio was defined as the ratio of malignant to nonmalignant prostate tissue. RESULTS AND LIMITATIONS: A total of 53 of 66 patients were eligible for analysis. mpMRI, PET, and PET/MRI detected cancer in 66% (35 of 53), 92% (49 of 53), and 98% (52 of 53) of the patients, respectively. Overall, 202 of 318 sextants (63.5%) contained cancer at pathologic examination. Simultaneous PET/MRI statistically outperformed mpMRI (area under the curve [AUC]: 0.88 vs 0.73; p<0.001) and PET imaging (AUC: 0.88 vs 0.83; p=0.002) for localization of PCa. Compared with mpMRI, PET imaging was more accurate (AUC: 0.83 vs 0.73; p=0.003). PET provided a high uptake ratio between malignant versus nonmalignant tissue (5.02 [range: 0.89-29.8]), but no significant correlation was observed between quantitative PET parameters and Gleason score or prostate-specific antigen value. CONCLUSIONS: Simultaneous 68Ga-PSMA HBED-CC PET/MRI improves diagnostic accuracy for PCa localization both compared with mpMRI and with PET imaging alone. Further prospective studies are warranted to evaluate its potential (eg, for biopsy guidance). PATIENT SUMMARY: We examined gallium 68 (68Ga)-prostate-specific membrane antigen (PSMA) HBED-CC positron emission tomography/magnetic resonance imaging (PET/MRI) for primary prostate cancer (PCa) and compared it with multiparametric MRI and PET alone. Our results indicate a higher diagnostic accuracy for 68Ga-PSMA HBED-CC PET/MRI that may help localize PCa.

Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

PURPOSE: Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). PROCEDURES: We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. RESULTS: The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C]CHO. The T/M ratio as well as the T/B ratio for [(18)F]Bombesin were significantly higher compared to those for [(11)C]CHO (p < 0.001, respectively). Kidney and liver uptake was statistically significantly lower for [(18)F]Bombesin (K/B 3.41 ± 0.81, L/B 1.99 ± 0.38) compared to [(11)C]CHO [K/B 7.91 ± 1.85 (p < 0.001), L/B 6.27 ± 1.99 (p < 0.001)]. The magnitudes of the time course of T/M and T/B ratios (T/M and T/Bdyn ratios) were statistically significantly different (showing a higher uptake of [(18)F]Bombesin compared to [(11)C]CHO); additionally, also the change of the T/M and T/B ratios over time was significantly different between both tracers in the dynamic analysis (p < 0.001, respectively). Furthermore, there was a statistically significantly different change of the K/B and L/B ratios over time between the two tracers in the dynamic analysis (p = 0.026 and p < 0.001, respectively). CONCLUSIONS: [(18)F]Bombesin (BAY 86-4367) visually and semi-quantitatively outperforms [(11)C]CHO in the PC-3 prostate cancer xenograft model. [(18)F]Bombesin tumor uptake was significantly higher compared to [(11)C]CHO. [(18)F]Bombesin showed better imaging properties compared to the clinically utilized [(11)C]CHO due to a higher tumor uptake as well as a lower liver and kidney uptake.

Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer.

PURPOSE: Current standard imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Recently ligands of PSMA (prostate specific membrane antigen) were introduced in PET (positron emission tomography) of prostate cancer. Thus the aims of this retrospective analysis were to 1) investigate the diagnostic efficacy of (68)Ga-PSMA-PET imaging for lymph node staging in patients with prostate cancer scheduled for radical prostatectomy and 2) compare it to morphological imaging (computerized tomography and magnetic resonance tomography) with histopathological evaluation as the standard of reference. MATERIALS AND METHODS: A total of 130 patients with intermediate to high risk prostate cancer were staged with (68)Ga-PSMA-PET/magnetic resonance tomography or PET/computerized tomography from December 2012 to November 2014 before radical prostatectomy and template pelvic lymph node dissection. Histopathological findings of resected tissue were statistically correlated with the results of (68)Ga-PSMA-PET and morphological imaging in a patient and template based manner. RESULTS: Lymph node metastases were found in 41 of 130 patients (31.5%). On patient based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 65.9%, 98.9% and 88.5%, and those of morphological imaging were 43.9%, 85.4% and 72.3%, respectively. Of 734 dissected lymph node templates 117 (15.9%) showed metastases. On template based analysis the sensitivity, specificity and accuracy of (68)Ga-PSMA-PET were 68.3%, 99.1% and 95.2%, and those of morphological imaging were 27.3%, 97.1% and 87.6%, respectively. On ROC analysis (68)Ga-PSMA-PET performed significantly better than morphological imaging alone on patient and template based analyses (p = 0.002 and <0.001, respectively). CONCLUSIONS: In patients with intermediate to high risk prostate cancer preoperative lymph node staging with (68)Ga-PSMA-PET proved to be superior to standard routine imaging. Thus it has the potential to replace current standard imaging for this indication if confirmed by prospective studies.

Discrimination Between Brown and White Adipose Tissue Using a 2-Point Dixon Water-Fat Separation Method in Simultaneous PET/MRI.

UNLABELLED: The purpose of the study was to evaluate signal-fat-fraction (SFF) analysis based on a 2-point-Dixon water-fat separation method in whole-body simultaneous PET/MR imaging for identifying brown adipose tissue (BAT) and discriminating it from white adipose tissue (WAT) using cross-validation via PET. METHODS: This retrospective, internal review board-approved study evaluated 66 PET/MR imaging examinations of 33 pediatric patients (mean age, 14.7 y; range, 7.4-21.4 y). Eleven elderly patients were evaluated as controls (mean age, 79.9 y; range, 76.3-88.6 y). Pediatric patients were divided into 2 groups: with and without metabolically active supraclavicular BAT. The standard of reference for the presence of BAT was at least 1 PET examination showing (18)F-FDG uptake. PET/MR imaging included a 2-point Dixon water-fat separation method. Signal intensities in regions of interest on fat and water images and mean standardized uptake values (SUVmean) were determined bilaterally in supraclavicular and gluteal fat depots. SFF was calculated from the ratio of fat signal over summed water and fat signal. Statistical analysis was conducted using the Student t test and correlation analysis. RESULTS: SFF was significantly lower (P < 0.0001) in supraclavicular BAT than gluteal WAT in all pediatric subjects. Supraclavicular SFF was significantly higher in the control than in the pediatric group (P < 0.0001). In PET-positive patients with multiple examinations, SFF stayed stable whereas SUVmean fluctuated (median intraindividual change, 5% vs. 91%). No significant correlation between SUVmean and SFF could be observed for BAT. CONCLUSION: The results demonstrate that MR imaging-SFF analysis is a reproducible imaging modality for the detection of human BAT and discrimination from WAT. SFF values of BAT are independent from its metabolic activity, making SFF a more reliable parameter for BAT than the commonly used PET signal. However, with the intent to investigate both the composition of BAT and its activation status, hybrid PET/MR imaging might provide supplemental information.

Categorical versus continuous circulating tumor cell enumeration as early surrogate marker for therapy response and prognosis during docetaxel therapy in metastatic prostate cancer patients.

BACKGROUND: Circulating tumor cell (CTCs) counts might serve as early surrogate marker for treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. We prospectively assessed categorical and continuous CTC-counts for their utility in early prediction of radiographic response, progression-free (PFS) and overall survival (OS) in mCRPC patients treated with docetaxel. METHODS: CTC-counts were assessed in 122 serial samples, as continuous or categorical (<5 vs. ≥5 CTCs) variables, at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles of docetaxel (3-weekly, 75 mg/m2) in 33 mCRPC patients. Treatment response (TR) was defined as non-progressive (non-PD) and progressive disease (PD), by morphologic RECIST or clinical criteria at q4 and q10. Binary logistic and Cox proportional hazards regression analyses were used as statistical methods. RESULTS: Categorical CTC-count status predicted PD at q4 already after one cycle (q1) and after 4 cycles (q4) of chemotherapy with an odds ratio (OR) of 14.9 (p=0.02) and 18.0 (p=0.01). Continuous CTC-values predicted PD only at q4 (OR 1.04, p=0.048). Regarding PFS, categorical CTC-counts at q1 were independent prognostic markers with a hazard ratio (HR) of 3.85 (95% CI 1.1-13.8, p=0.04) whereas early continuous CTC-values at q1 failed significance (HR 1.02, 95% CI 0.99-1.05, p=0.14). For OS early categorical and continuous CTC-counts were independent prognostic markers at q1 with a HR of 3.0 (95% CI 1.6-15.7, p=0.007) and 1.02 (95% CI 1.0-1.040, p=0.04). CONCLUSIONS: Categorical CTC-count status is an early independent predictor for TR, PFS and OS only 3 weeks following treatment initiation with docetaxel whereas continuous CTC-counts were an inconsistent surrogate marker in mCRPC patients. For clinical practice, categorical CTC-counts may provide complementary information towards individualized treatment strategies with early prediction of treatment efficacy and optimized sequential treatment.

Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy.

UNLABELLED: The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of (68)Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. METHODS: Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2-59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of (68)Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. RESULTS: Two hundred twenty-two (89.5%) patients showed pathologic findings in (68)Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, and 0.2 to <0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in <1, 1 to <2, 2 to <5, and ≥5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in >6, 4-6, and <4 mo, respectively). (68)Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (≤7 vs. ≥8), detection efficacy was significantly increased (P = 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P = 0.0783). CONCLUSION: Hybrid (68)Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (<0.5 ng/mL), which in many cases can substantially influence the further clinical management.

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.

Evaluation of 18F-fluoride PET/MR and PET/CT in patients with foot pain of unclear cause.

UNLABELLED: Our objective was to compare the quality and diagnostic performance of (18)F-fluoride PET/MR imaging with that of (18)F-fluoride PET/CT imaging in patients with foot pain of unclear cause. METHODS: Twenty-two patients (9 men, 13 women; mean age, 48 ± 18 y; range, 20-78 y) were prospectively included in this study and underwent a single-injection dual-imaging protocol with (18)F-fluoride PET/CT and PET/MR. At a minimum, the PET/MR protocol included T1-weighted spin echo and proton-density fat-saturated sequences in 2 planes each with simultaneous acquisition of PET over 20 min. PET/CT included a native isotropic (0.6 mm) diagnostic CT scan (80 kV, 165 mAs) and a subsequent PET scan (2 min per bed position). By consensus, 2 masked interpreters randomly assessed both PET datasets for image quality (3-point scale) and for the presence of focal lesions with increased (18)F-fluoride uptake (maximum of 4 lesions). For each dataset (PET/CT vs. PET/MR), the diagnoses were defined using both PET and a morphologic dataset. Standardized uptake values (SUVs) from the 2 devices were compared using linear correlation and Bland-Altman plots. Moreover, we estimated the potential for dose reduction for PET/MR compared with PET/CT considering the longer acquisition time of PET/MR analyzing count rate statistics. RESULTS: Image quality was rated diagnostic for both PET datasets. However, with a mean rating of 3.0/3 for PET/MR and 2.3/3 for PET/CT, image quality was significantly superior for PET/MR (P < 0.0001). The sensitivity of the PET datasets in PET/MR and PET/CT was equivalent, with the same 42 lesions showing focal (18)F-fluoride uptake. In PET/MR, the mean SUVmean was 10.4 (range, 2.0-67.7) and the mean SUVmax was 15.6 (range, 2.9-94.1). In PET/CT, the corresponding mean SUVmean of PET/CT was 10.2 (range, 1.8-55.6) and the mean SUVmax was 16.3 (range, 2.5-117.5), resulting in a high linear correlation coefficient (r = 0.96, P < 0.0001, for SUVmean and for SUVmax). A final consensus interpretation revealed the most frequent main diagnoses to be osteoarthritis, stress fracture, and bone marrow edema. PET/CT was more precise in visualizing osteoarthritis, whereas PET/MR was more specific in nondegenerative pathologies because of the higher soft-tissue and bone marrow contrast. The longer acquisition time of MR compared with CT would potentially allow (18)F-fluoride dose reduction using hybrid (18)F-fluoride PET/MR imaging of at least 50% according to the counting rate analysis. CONCLUSION: In patients with foot pain of unclear cause, (18)F-fluoride PET/MR is technically feasible and is more robust in terms of image quality and SUV quantification than (18)F-fluoride PET/CT. In most patients, (18)F-fluoride PET/MR provided more diagnostic information at a higher diagnostic certainty than did PET/CT. Thus, PET/MR combines the high sensitivity of (18)F-fluoride PET to pinpoint areas with the dominant disease activity and the specificity of MR imaging for the final diagnosis with the potential for a substantial dose reduction compared with PET/CT.

Motion correction strategies for integrated PET/MR.

UNLABELLED: Integrated whole-body PET/MR facilitates the implementation of a broad variety of respiratory motion correction strategies, taking advantage of the strengths of both modalities. The goal of this study was the quantitative evaluation with clinical data of different MR- and PET-data-based motion correction strategies for integrated PET/MR. METHODS: The PET and MR data of 20 patients were simultaneously acquired for 10 min on an integrated PET/MR system after administration of (18)F-FDG or (68)Ga-DOTANOC. Respiratory traces recorded with a bellows were compared against MR self-gating signals and signals extracted from PET raw data with the sensitivity method, by applying principal component analysis (PCA) or Laplacian eigenmaps and by using a novel variation combining the former and either of the latter two. Gated sinograms and MR images were generated accordingly, followed by image registration to derive MR motion models. Corrected PET images were reconstructed by incorporating this information into the reconstruction. An optical flow algorithm was applied for PET-based motion correction. Gating and motion correction were evaluated by quantitative analysis of apparent tracer uptake, lesion volume, displacement, contrast, and signal-to-noise ratio. RESULTS: The correlation between bellows- and MR-based signals was 0.63 ± 0.19, and that between MR and the sensitivity method was 0.52 ± 0.26. Depending on the PET raw-data compression, the average correlation between MR and PCA ranged from 0.25 ± 0.30 to 0.58 ± 0.33, and the range was 0.25 ± 0.30 to 0.42 ± 0.34 if Laplacian eigenmaps were applied. By combining the sensitivity method and PCA or Laplacian eigenmaps, the maximum average correlation to MR could be increased to 0.74 ± 0.21 and 0.70 ± 0.19, respectively. The selection of the best PET-based signal for each patient yielded an average correlation of 0.80 ± 0.13 with MR. Using the best PET-based respiratory signal for gating, mean tracer uptake increased by 17 ± 19% for gating, 13 ± 10% for MR-based motion correction, and 18 ± 15% for PET-based motion correction, compared with the static images. Lesion volumes were 76 ± 31%, 83 ± 18%, and 74 ± 22% of the sizes in the static images for gating, MR-based motion correction, and PET-based motion correction, respectively. CONCLUSION: Respiratory traces extracted from MR and PET data are comparable to those based on external sensors. The proposed PET-driven gating method improved respiratory signals and overall stability. Consistent results from MR- and PET-based correction methods enable more flexible PET/MR scan protocols while achieving higher PET image quality.

Self-gated MRI motion modeling for respiratory motion compensation in integrated PET/MRI.

Accurate localization and uptake quantification of lesions in the chest and abdomen using PET imaging is challenged by respiratory motion occurring during the exam. This work describes how a stack-of-stars MRI acquisition on integrated PET/MRI systems can be used to derive a high-resolution motion model, how many respiratory phases need to be differentiated, how much MRI scan time is required, and how the model is employed for motion-corrected PET reconstruction. MRI self-gating is applied to perform respiratory gating of the MRI data and simultaneously acquired PET raw data. After gated PET reconstruction, the MRI motion model is used to fuse the individual gates into a single, motion-compensated volume with high signal-to-noise ratio (SNR). The proposed method is evaluated in vivo for 15 clinical patients. The gating requires 5-7 bins to capture the motion to an average accuracy of 2mm. With 5 bins, the motion-modeling scan can be shortened to 3-4 min. The motion-compensated reconstructions show significantly higher accuracy in lesion quantification in terms of standardized uptake value (SUV) and different measures of lesion contrast compared to ungated PET reconstruction. Furthermore, unlike gated reconstructions, the motion-compensated reconstruction does not lead to SNR loss.

Comparison of [¹¹C]choline ([¹¹C]CHO) and S(+)-ß-methyl-[¹¹C]choline ([¹¹C]SMC) as imaging probes for prostate cancer in a PC-3 prostate cancer xenograft model.

PURPOSE: Carbon-11- and fluorine-18-labeled choline derivatives have been introduced as promising tracers for prostate cancer imaging. However, due to limited specificity and sensitivity, there is a need for new tracers with higher sensitivity and specificity for diagnosing prostate cancer to improve tracer uptake and enhance imaging contrast. The aim of this study was to compare the properties of [(11)C]choline ([(11)C]CHO) with S(+)-ß-methyl-[(11)C]choline ([(11)C]SMC) as tracer for prostate cancer imaging in a human prostate tumor mouse xenograft model by small-animal positron emission tomography/X-ray computed tomography (PET/CT). PROCEDURES: We carried out a dual-tracer small-animal PET/CT study comparing [(11)C]CHO and [(11)C]SMC. The androgen-independent human prostate tumor cell line PC3 was implanted subcutaneously in the flanks of Naval Medical Research Institute (NMRI) (nu/nu) mice (n = 11). Mice-6 weeks post-xenograft implantation-were injected with 37 MBq [(11)C]CHO via the tail vein. On a separate day, the mice were injected with 37 MBq [(11)C]SMC. Dynamic imaging was performed for 60 min with the Inveon animal PET/CT scanner (Siemens Medical Solutions) on two separate days (randomizing the sequence of the tracers). The dynamic PET images were acquired in list mode. Regions of interest (5 × 5 × 5 mm) were placed in transaxial slices in tumor, muscle (thigh), liver, kidney, and blood. Image analysis was performed calculating tumor to muscle (T/M) ratios based on summed images as well as dynamic data. RESULTS: For [(11)C]SMC, the mean T/M ratio was 2.24 ± 0.56 while the corresponding mean [(11)C]CHO T/M ratio was 1.35 ± 0.28. The T/M ratio for [(11)C]SMC was significant higher compared to [(11)C]CHO (p < 0.001). The time course of T/M ratio (T/Mdyn ratio) of [(11)C]SMC was higher compared to [(11)C]CHO with a statistically significant difference between the magnitudes of the T/M ratios and a significant different change of the T/M ratios over time between [(11)C]CHO and [(11)C]SMC. CONCLUSION: Our results demonstrate that [(11)C]SMC is taken up by the tumor in the PC-3 prostate cancer xenograft model. [(11)C]SMC uptake was significantly higher compared to the clinically utilized [(11)C]CHO tracer with a higher contrast allowing imaging of a prostate cancer xenograft.

Detection of liver metastases in patients with adenocarcinomas of the gastrointestinal tract: comparison of (18)F-FDG PET/CT and MR imaging.

PURPOSE: Aim of our study was to compare the diagnostic performance of (18)F-FDG PET/CT and MR imaging (MRI) in the detection of liver metastases in patients with adenocarcinomas of the gastrointestinal tract. METHODS: A total of 49 patients with adenocarcinomas of the gastrointestinal tract who had undergone (18)F-FDG PET/CT and MRI of the liver were included in this study. The MRI protocol included diffusion-weighted imaging and dynamic contrast-enhanced MR imaging after intravenous injection of Gd-DTPA. PET and MR images were analyzed by two experienced radiologists. Imaging results were correlated with histopathological findings or imaging follow-up as available. Sensitivities of both modalities were compared using McNemar Test. Receiver operating characteristic (ROC) curves were calculated to determine the diagnostic performance in correctly identifying liver metastases. RESULTS: A total of 151 metastases were confirmed. For lesion detection, MRI was significantly superior to (18)F-FDG PET/CT. Sensitivity of MRI in detecting metastases was 86.8% for Reader 1 (R1) and 87.4% for Reader 2 (R2), of PET/CT 66.2% for R1 and 68.2% for R2. Regarding only metastases with diameters of 10 mm or less, sensitivities of MRI were 66.7% for R1 and 75.0% for R2, and were significantly higher than those of PET/CT (17.9% for R1 and 20.5% for R2). ROC analysis showed superiority for lesion classification of MRI as compared to (18)F-FDG PET/CT. CONCLUSION: MRI is significantly superior to (18)F-FDG PET/CT in the detection and classification of liver metastases in patients with adenocarcinomas of the gastrointestinal tract, especially in the detection of small metastases.

Diagnostic value of retrospective PET-MRI fusion in head-and-neck cancer.

BACKGROUND: To assess the diagnostic value of retrospective PET-MRI fusion and to compare the results with side-by-side analysis and single modality use of PET and of MRI alone for locoregional tumour and nodal staging of head-and-neck cancer. METHODS: Thirty-three patients with head-and-neck cancer underwent preoperative contrast-enhanced MRI and PET/CT for staging. The diagnostic data of MRI, PET, side-by-side analysis of MRI and PET images and retrospective PET-MRI fusion were systematically analysed for tumour and lymph node staging using receiver operating characteristic (ROC) analysis. The results were correlated to the histopathological evaluation. RESULTS: The overall sensitivity/specificity for tumour staging for MRI, PET, side-by-side analysis and retrospective PET-MRI fusion was 79%/66%, 82%/100%, 86%/100% and 89%/100%, respectively. The overall sensitivity/specificity for nodal staging on a patient basis for MRI, PET, side-by-side analysis and PET-MRI fusion was 94%/64%, 94%/91%, 94%/82% and 94%/82%, respectively. MRI, PET, side-by-side analysis and retrospective image fusion were associated with correct diagnosis/over-staging/under-staging of N-staging in 70.4%/18.5%/11.1%, 81.5%/7.4%/11.1%, 81.5%/11.1%/7.4% and 81.5%/11.1%/7.4%, respectively.ROC analysis showed no significant differences in tumor detection between the investigated methods. The Area Under the Curve (AUC) for MRI, PET, side-by-side analysis and retrospective PET-MRI fusion were 0.667/0.667/0.702/0.708 (p > 0.05). The most reliable technique in detection of cervical lymph node metastases was PET imaging (AUC: 0.95), followed by side-by-side analysis and retrospective image fusion technique (AUC: 0.941), which however, was not significantly better then the MRI (AUC 0.935; p > 0.05). CONCLUSIONS: We found a beneficial use of multimodal imaging, compared with MRI or PET imaging alone, particular in individual cases of recurrent tumour disease. Side-by-side analysis and retrospective image fusion analysis did not perform significantly differently.

11C-Choline PET/pathology image coregistration in primary localized prostate cancer.

PURPOSE: The aim of this study was to develop a methodology for the comparison of pathology specimens after prostatectomy (post-S) with PET images obtained before surgery (pre-S). This method was used to evaluate the merit of (11)C-choline PET/CT for delineation of gross tumour volume (GTV) in prostate cancer (PC). METHODS: In 28 PC patients, (11)C-choline PET/CT was performed before surgery. PET/CT data were coregistered with the pathology specimens. GTV on PET images (GTV-PET) was outlined automatically and corrected manually. Tumour volume in the prostate (TVP) was delineated manually on the pathology specimens. Based on the coregistered PET/pathology images, the following parameters were assessed: SUVmax and SUVmean in the tumoral and nontumoral prostate (NP), GTV-PET (millilitres) and TVP (millilitres). RESULTS: PET/pathology image coregistration was satisfactory. Mean SUVmax in the TVP was lower than in the NP: 5.0 and 5.5, respectively (p = 0.093). Considering the entire prostate, SUVmax was located in the TVP in two patients, in the TVP and NP in 12 patients and exclusively in NP in 14 patients. Partial overlap the TVP and GTV-PET was seen in 71% of patients, and complete overlap in 4%. CONCLUSION: PET/pathology image coregistration can be used for evaluation of different imaging modalities. (11)C-Choline PET failed to distinguish tumour from nontumour tissue.

Prognostic value of 11C-choline PET/CT and CT for predicting survival of bladder cancer patients treated with radical cystectomy.

BACKGROUND: In patients with bladder cancer (BCa) preoperative staging with (11)C-choline positron emission tomography-computed tomography (PET/CT) could be used to derive prognostic information and hence stratify patients preoperatively with respect to disease management. METHODS: From June 2004 to May 2007, 44 patients with localized BCa were staged with (11)C-choline PET/CT before radical cystectomy. The results of imaging were correlated to overall survival (OS) and cumulative incidence of cancer-specific death (CSD). RESULTS: There was no statistically significant difference in OS and CSD between the patient groups when stratified for organ-confined versus non-organ-confined disease or lymph node involvement defined by either (11)C-choline PET/CT (OS: p = 0.262, hazard ratio [HR] = 1.60; p = 0.527, HR = 0.76; CSD: p = 0.144, HR = 2.25; p = 0.976, HR = 0.98) or CT (OS: p = 0.518, HR = 1.34; p = 0.228, HR = 1.67; CSD: p = 0.323, HR = 1.90; p = 0.136, HR = 2.38). The limitation of this study is the small number of included patients. CONCLUSION: In our prospective trial neither CT nor (11)C-choline PET/CT were able to sufficiently predict OS or CSD in BCa patients treated with radical cystectomy albeit trends and moderately increased HRs could be demonstrated without significant differences between CT or (11)C-choline PET/CT. However, these trends might prove statistically significant in bigger patient cohorts. Therefore initial transsectional imaging might be of clinical relevance in respect to prognosis and could play a role in the counseling of BCa patients.