Claudia Bacher-Stier

Thallium-201 gated single-photon emission tomography for the assessment of left ventricular ejection fraction and regional wall motion abnormalities in comparison with two-dimensional echocardiography

Abstract. Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n=55) or pharmacological stress (n=17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r=0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r=0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n=23), these correlations were even better (r=0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%–100% and 82%–98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.

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.

(S)-4-(3-18F-Fluoropropyl)-l-Glutamic Acid: An 18F-Labeled Tumor-Specific Probe for PET/CT Imaging—Dosimetry

The glutamic acid derivative (S)-4-(3-18F-Fluoropropyl)-l-glutamic acid (18F-FSPG, alias BAY 94-9392), a new PET tracer for the detection of malignant diseases, displayed promising results in non–small cell lung cancer patients. The aim of this study was to provide dosimetry estimates for 18F-FSPG based on human whole-body PET/CT measurements. Methods: 18F-FSPG was prepared by a fully automated 2-step procedure and purified by a solid-phase extraction method. PET/CT scans were obtained for 5 healthy volunteers (mean age, 59 y; age range, 51–64 y; 2 men, 3 women). Human subjects were imaged for up to 240 min using a PET/CT scanner after intravenous injection of 299 ± 22.5 MBq of 18F-FSPG. Image quantification, time–activity data modeling, estimation of normalized number of disintegrations, and production of dosimetry estimates were performed using the RADAR (RAdiation Dose Assessment Resource) method for internal dosimetry and in general concordance with the methodology and principles as presented in the MIRD 16 document. Results: Because of the renal excretion of the tracer, the absorbed dose was highest in the urinary bladder wall and kidneys, followed by the pancreas and uterus. The individual organ doses (mSv/MBq) were 0.40 ± 0.058 for the urinary bladder wall, 0.11 ± 0.011 for the kidneys, 0.077 ± 0.020 for the pancreas, and 0.030 ± 0.0034 for the uterus. The calculated effective dose was 0.032 ± 0.0034 mSv/MBq. Absorbed dose to the bladder and the effective dose can be reduced significantly by frequent bladder-voiding intervals. For a 0.75-h voiding interval, the bladder dose was reduced to 0.10 ± 0.012 mSv/MBq, and the effective dose was reduced to 0.015 ± 0.0010 mSv/MBq. Conclusion: On the basis of the distribution and biokinetic data, the determined radiation dose for 18F-FSPG was calculated to be 9.5 ± 1.0 mSv at a patient dose of 300 MBq, which is of similar magnitude to that of 18F-FDG (5.7 mSv). The effective dose can be reduced to 4.5 ± 0.30 mSv (at 300 MBq), with a bladder-voiding interval of 0.75 h.

Abstract 4139: Diagnostic performance of the F-18 labeled bombesin analog BAY 86-4367 in patients with primary prostate cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Purpose: BAY 86-4367 is a new directly F-18 labeled, synthetic bombesin analog (3-Cyano-4-[18F]fluorobenzoyl-Ala(SO3H)-Ala(SO3H)-Ava-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH2) with antagonistic properties, targeting Gastrin-releasing-peptide receptors (GRPr). The aim of this proof of mechanism (PoM) study is to demonstrate the feasibility, safety, tolerability, biodistribution and diagnostic performance of the PET tracer BAY 86-4367 in patients with primary prostate cancer. Methods: 5 patients with non-treated primary prostate cancer (PSA range 7 to 24 µg/l) were prospectively included in the study. All patients had standardized biopsy proven primary prostate cancer with Gleason scores ranging from 6 (3+3) to 9 (4+5). All patients had standardized sequential dynamic and static PET/CT using the F-18 labeled tracer BAY 86-4367 for primary staging. Safety data (vital signs, ECG, adverse effects) were assessed in all patients. Four patients had a prior PET/CT scan with F-18 choline. Patients were scheduled for prostatectomy of primary prostate cancer. Full prostate samples were histopathologically analyzed to further confirm the imaging localisation data. Results: The tracer BAY 86-4367 was well tolerated after injection of ∼300 MBq and a peptide mass dose <40 µg per patient. Safety data showed no relevant changes in the sequential blood values, electrocardiograms, urine testing or physical examination. Malignant lesions were depicted in 3/5 patients with the F-18 labeled BAY 86-4367 tracer. Biopsy verified the correct tumor localisation of these imaging findings. In two patients with histologically proven primary prostate cancer, BAY 86-4367 showed no active accumulation in the prostate. F-18 choline PET/CT was performed in 4/5 patients with positive signals in all 4 patients. Correlation with biopsy showed correct localisation of F-18 choline in tumor tissue. However, there was false positive F-18 choline accumulation in benign hyperplasia of the prostate. Conclusion: PET imaging with the F-18 labeled bombesin analog BAY 86-4367 is safe. The tracer BAY 86-4367 correctly depicts primary prostate cancer in a subset of patients. However, diagnostic accuracy of bombesin analogs in GRPr imaging needs to be further explored. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4139. doi:10.1158/1538-7445.AM2011-4139