Bert-Ram Sah

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). Methods: Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new 18F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with 18F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. Results: Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7–4.9 mSv). Conclusion: BAY 864367, a novel 18F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging.

Computed tomographic perfusion imaging for the prediction of response and survival to transarterial radioembolization of liver metastases.

PurposeThe purpose of this study was to evaluate prospectively, in patients with liver metastases, the ability of computed tomographic (CT) perfusion to predict the morphologic response and survival after transarterial radioembolization (TARE). MethodsThirty-eight patients (22 men; mean [SD] age, 63 [12] years) with otherwise therapy-refractory liver metastases underwent dynamic, contrast-enhanced CT perfusion within 1 hour before treatment planning catheter angiography, for calculation of the arterial perfusion (AP) of liver metastases, 20 days before TARE with Yttrium-90 microspheres. Treatment response was evaluated morphologically on follow-up imaging (mean, 114 days) on the basis of the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). Pretreatment CT perfusion was compared between responders and nonresponders. One-year survival was calculated including all 38 patients using the Kaplan-Meier curves; the Cox proportional hazard model was used for calculating predictors of survival. ResultsFollow-up imaging was not available in 11 patients because of rapidly deteriorating health or death. From the remaining 27, a total of 9 patients (33%) were classified as responders and 18 patients (67%) were classified as nonresponders. A significant difference in AP was found on pretreatment CT perfusion between the responders and the nonresponders to the TARE (P < 0.001). Change in tumor size on the follow-up imaging correlated significantly and negatively with AP before the TARE (r = −0.60; P = 0.001). Receiver operating characteristics analysis of AP in relation to treatment response revealed an area under the curve of 0.969 (95% confidence interval, 0.911–1.000; P < 0.001). A cutoff AP of 16 mL per 100 mL/min was associated with a sensitivity of 100% (9/9) (95% CI, 70%–100%) and a specificity of 89% (16/18) (95% CI, 62%–96%) for predicting therapy response. A significantly higher 1-year survival after the TARE was found in the patients with a pretreatment AP of 16 mL per 100 mL/min or greater (P = 0.028), being a significant, independent predictor of survival (hazard ratio, 0.101; P = 0.015). ConclusionsArterial perfusion of liver metastases, as determined by pretreatment CT perfusion imaging, enables prediction of short-term morphologic response and 1-year survival to TARE.

Impact of a new motion-correction algorithm on image quality of low-dose coronary CT angiography in patients with insufficient heart rate control.

RATIONALE AND OBJECTIVES Prospective electrocardiogram (ECG) triggering allows coronary computed tomography angiography (CCTA) scanning with low radiation dose but requires heart rates below 63 beats/min. We assessed the impact of a novel vendor-specific motion-correction algorithm on image quality and interpretability of low-dose CCTA acquired despite insufficient heart rate control. MATERIALS AND METHODS In 40 patients undergoing CCTA for the assessment of known or suspected coronary artery disease who did not reach the target heart rate below 63 beats/min despite β-blockade before prospective low-dose scanning, the temporal acquisition window was increased (80 ms additional padding). The new algorithm detects and integrates vessel path and velocity from adjacent cardiac phases for motion correction. Two blinded observers assessed image quality on a 4-point Likert scale (1, nonevaluative; 2, reduced but evaluative; 3, good; and 4, excellent) and the fraction of interpretable segments (score 2 or more) using motion correction versus standard reconstruction. RESULTS Image reconstruction with motion correction resulted in an increased median coronary artery image quality score (excellent interobserver agreement, κ = 0.85) compared to standard reconstruction (3.4 vs. 3.0, P < .001). Consequently, motion-corrected reconstruction significantly improved the overall interpretability of coronary arteries (from 78% to 88%, P < .001). Estimated mean effective radiation dose was 2.3 ± 0.8 mSv. CONCLUSIONS A novel, vendor-specific, motion-corrected, reconstruction algorithm improves image quality and interpretability of prospectively ECG-triggered low-dose CCTA despite insufficient heart rate control.

Early Treatment Response Evaluation after Yttrium-90 Radioembolization of Liver Malignancy with CT Perfusion

PURPOSE To evaluate computed tomography (CT) perfusion for assessment of early treatment response after transarterial radioembolization of patients with liver malignancy. MATERIALS AND METHODS Dynamic contrast-enhanced CT liver perfusion was performed before and 4 weeks after transarterial radioembolization in 40 patients (25 men and 15 women; mean age, 64 y ± 11; range, 35-80 y) with liver metastases (n = 27) or hepatocellular carcinoma (HCC) (n = 13). Arterial perfusion (AP) of tumors derived from CT perfusion and tumor diameters were measured on CT perfusion before and after transarterial radioembolization. Success of transarterial radioembolization was evaluated on morphologic follow-up imaging (median follow-up time, 4 mo) based on Response Evaluation Criteria in Solid Tumors (Version 1.1). CT perfusion parameters before and after transarterial radioembolization for different response groups were compared. Kaplan-Meier curves were plotted to illustrate overall 1-year survival rates. RESULTS Liver metastases showed significant differences in AP before and after transarterial radioembolization in responders (P < .05) but not in nonresponders (P = .164). In HCC, AP values before and after transarterial radioembolization were not significantly different in responders and nonresponders (P = .180 and P = .052). Tumor diameters were not significantly different on CT perfusion before and after transarterial radioembolization in responders and nonresponders with liver metastases and HCC (P = .654, P = .968, P = .148, P = .164). In patients with significant decrease of AP in liver metastases after transarterial radioembolization, 1-year overall survival was significantly higher than in patients showing no reduction of AP. CONCLUSIONS CT perfusion showed early reduction of AP in liver metastases responding to transarterial radioembolization; tumor diameter remained unchanged early after treatment. No significant early treatment response to transarterial radioembolization was found in patients with HCC. In patients with liver metastases, a decrease of AP after transarterial radioembolization was associated with a higher 1-year overall survival rate.

Tumor Imaging in Patients with Advanced Tumors Using a New 99mTc-Radiolabeled Vitamin B12 Derivative

Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new 99mTc-cobalamin derivative (99mTc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, 99mTc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of 99mTc-PAMA-cobalamin in 10 patients with various metastatic tumors. Methods: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300–500 MBq of 99mTc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3–10 received between 20 and 1,000 μg of cobalamin intravenously before injection of 99mTc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma. Results: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on 99mTc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20–100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient. Conclusion: To our knowledge, we report for the first time on 99mTc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible.

18F-FDG-PET/CT FOR THERAPY CONTROL IN VASCULAR GRAFT INFECTIONS: A FIRST FEASIBILITY STUDY

The aim of this study was to evaluate the clinical value of PET/CT with 18F-FDG for therapy control in patients with prosthetic vascular graft infections (PVGIs). Methods: In this single-center, observational, prospective cohort study, 25 patients with a median age of 66 y (range, 48–81 y) who had a proven PVGI were included. Follow-up 18F-FDG PET/CT was performed at a median of 170 d (range, 89–249 d) after baseline examination. Two independent and masked interpreters measured maximum standardized uptake values to quantify metabolic activity and analyzed whole-body datasets for a secondary diagnosis (i.e., infectious foci not near the graft). The metabolic activity of the graft was correlated with clinical information and 2 laboratory markers (C-reactive protein and white blood cell count). Results: 18F-FDG PET/CT had an impact on management in all patients. In 19 of 25 patients (76%), antibiotic treatment was continued because of the results of follow-up 18F-FDG PET/CT. Antibiotic treatment was stopped or changed in 8% and 16% of patients, respectively. In 8 patients (32%), additional incidental findings were detected on follow-up 18F-FDG PET/CT and had a further impact on patient management. Only in a subgroup of patients with PVGI and no other sites of infection was a significant correlation found between the difference in C-reactive protein at the time of baseline and follow-up 18F-FDG PET/CT and the difference in maximum standardized uptake value (n = 11; R2 = 0.67; P = 0.002). Conclusion: 18F-FDG PET/CT represents a useful tool in therapy monitoring of PVGI and has an impact on patient management.

PET/MR Outperforms PET/CT in Suspected Occult Tumors.

Background To compare the diagnostic accuracy of PET/MR and PET/CT in patients with suspected occult primary tumors. Methods This prospective study was approved by the institutional review board. Sequential PET/CT-MR was performed in 43 patients (22 male subjects; median age, 58 years; range, 20-86 years) referred for suspected occult primary tumors. Patients were assessed with PET/CT and PET/MR for the presence of a primary tumor, lymph node metastases, and distant metastases. Wilcoxon signed-rank test was performed to compare the diagnostic accuracy of PET/CT and PET/MR. Result According to the standard of reference, a primary lesion was found in 14 patients. In 16 patients, the primary lesion remained occult. In the remaining 13 patients, lesions proved to be benign. PET/MR was superior to PET/CT for primary tumor detection (sensitivity/specificity, 0.85/0.97 vs 0.69/0.73; P = 0.020) and comparable to PET/CT for the detection of lymph node metastases (sensitivity/specificity, 0.93/1.00 vs 0.93/0.93; P = 0.157) and distant metastases (sensitivity/specificity, 1.00/0.97 vs 0.82/1.00; P = 0.564). PET/CT tended to misclassify physiologic FDG uptake as malignancy compared with PET/MR (8 patients vs 1 patient). Conclusions PET/MR outperforms PET/CT in the workup of suspected occult malignancies. PET/MR may replace PET/CT to improve clinical workflow.

Clinical evaluation of a block sequential regularized expectation maximization reconstruction algorithm in 18F-FDG PET/CT studies

Purpose To investigate the clinical performance of a block sequential regularized expectation maximization (BSREM) penalized likelihood reconstruction algorithm in oncologic PET/computed tomography (CT) studies. Methods A total of 410 reconstructions of 41 fluorine-18 fluorodeoxyglucose-PET/CT studies of 41 patients with a total of 2010 lesions were analyzed by two experienced nuclear medicine physicians. Images were reconstructed with BSREM (with four different &bgr; values) or ordered subset expectation maximization (OSEM) algorithm with/without time-of-flight (TOF/non-TOF) corrections. OSEM reconstruction postfiltering was 4.0 mm full-width at half-maximum; BSREM did not use postfiltering. Evaluation of general image quality was performed with a five-point scale using maximum intensity projections. Artifacts (category 1), image sharpness (category 2), noise (category 3), and lesion detectability (category 4) were analyzed using a four-point scale. Size and maximum standardized uptake value (SUVmax) of lesions were measured by a third reader not involved in the image evaluation. Results BSREM-TOF reconstructions showed the best results in all categories, independent of different body compartments. In all categories, BSREM non-TOF reconstructions were significantly better than OSEM non-TOF reconstructions (P<0.001). In almost all categories, BSREM non-TOF reconstruction was comparable to or better than the OSEM-TOF algorithm (P<0.001 for general image quality, image sharpness, noise, and P=1.0 for artifact). Only in lesion detectability was OSEM-TOF significantly better than BSREM non-TOF (P<0.001). Both BSREM-TOF and BSREM non-TOF showed a decreasing SUVmax with increasing &bgr; values (P<0.001) and TOF reconstructions showed a significantly higher SUVmax than non-TOF reconstructions (P<0.001). Conclusion The BSREM reconstruction algorithm showed a relevant improvement compared with OSEM reconstruction in PET/CT studies in all evaluated categories. BSREM might be used in clinical routine in conjunction with TOF to achieve better/higher image quality and lesion detectability or in PET/CT-systems without TOF-capability for enhancement of overall image quality as well.

Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin.

ObjectivesThere is uncertainty about patient selection and the adequate timing at which fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) is indicated in the diagnostic work-up of fever of unknown origin (FUO). The aim of this study was to determine the diagnostic performance of 18F-FDG PET/CT in patients with FUO. MethodsAll consecutive patients who underwent 18F-FDG PET/CT at the University Hospital Zurich because of FUO between 2006 and 2012 were included in this retrospective, observational study. ResultsA total of 76 patients [70% men, median (interquartile range) age 60 (47–67) years] were included. 18F-FDG PET/CT showed characteristically increased 18F-FDG activity in 56 patients (74%), leading to confirmation of or change in the suspected cause of FUO in 57 and 17%, respectively. The final diagnosis after 18F-FDG PET/CT included infection (21%), malignancy (22%), noninfectious inflammatory disease (12%), others (5%), or an unknown cause (40%). The success rate, sensitivity, and specificity of 18F-FDG PET/CT were 60, 77, and 31%, respectively. Sensitivity was highest in patients with suspected malignancy (100%, 95% confidence interval 79–100%). Diagnostic performance was independent of the investigated variables other than suspected infection as a cause of FUO (odds ratio 0.1, 95% confidence interval 0.01–0.8, P=0.033). ConclusionThe diagnostic performance of 18F-FDG PET/CT was significantly higher in patients with suspected malignancy causing a FUO compared with suspected infection or noninfectious inflammatory disease. However, it was independent of the baseline characteristics and duration of fever. This supports the recommendation to perform 18F-FDG PET/CT early in the diagnostic work-up of FUO, which may shorten disease duration and lower health costs, particularly when infection or malignancy is suspected.

Attenuation Correction Maps for SPECT Myocardial Perfusion Imaging from Contrast-Enhanced Coronary CT Angiography: Gemstone Spectral Imaging with Single-Source Dual Energy and Material Decomposition

The aim of this study was to explore the feasibility of attenuation correction (AC) of myocardial perfusion imaging (MPI) with a virtual unenhanced cardiac CT scan synthesized from contrast-enhanced single-source dual-energy coronary CT angiography. Methods: Segmental myocardial percentage uptake values obtained with AC were analyzed by use of correlation analysis and Bland–Altman limits of agreement (20-segment model), and clinical agreement was evaluated in 30 patients. Results: The 2 methods showed an excellent correlation for segmental myocardial percentage uptake at stress (r = 0.93; P < 0.001; low dose) and at rest (r = 0.90; P < 0.001; high dose) with narrow Bland–Altman limits of agreement (−6.8% to 7.8% and −7.8% to 7.4%, respectively). The levels of clinical agreement of SPECT MPI corrected with standard versus virtual unenhanced CT AC were 99% per coronary territory and 97% per patient. Conclusion: Our results suggest that AC of SPECT MPI with a virtual unenhanced CT scan synthesized from contrast-enhanced coronary CT angiography is feasible and reliable.