First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy.

Purpose: To report on the first-in-human phase I study of VIP152 (NCT02635672), a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor.

Patients And Methods: Adults with solid tumors or aggressive non-Hodgkin lymphoma who were refractory to or had exhausted all available therapies received VIP152 monotherapy as a 30-minute intravenous, once-weekly infusion, as escalating doses (5, 10, 15, 22.5, or 30 mg in 21-day cycles) until the MTD was determined.

Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer.

Selective inhibition of exclusively transcription-regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY-958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited the best overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats.

Parametric Binding Images of the TSPO Ligand 18F-DPA-714.

Unlabelled: F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of F-DPA-714 binding.

Methods: Ninety-minute dynamic F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used.

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

Unlabelled: 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 (18)F-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.

Quantification of [18F]DPA-714 binding in the human brain: initial studies in healthy controls and Alzheimer's disease patients.

Fluorine-18 labelled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-yl)acetamide ([(18)F]DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of [(18)F]DPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq [(18)F]DPA-714.

Positron emission tomography imaging of the 18-kDa translocator protein (TSPO) with [18F]FEMPA in Alzheimer's disease patients and control subjects.

Purpose: Imaging of the 18-kDa translocator protein (TSPO) is a potential tool for examining microglial activation and neuroinflammation in early Alzheimer's disease (AD). [(18)F]FEMPA is a novel high-affinity second-generation TSPO radioligand that has displayed suitable pharmacokinetic properties in preclinical studies. The aims of this study were to quantify the binding of [(18)F]FEMPA to TSPO in AD patients and controls and to investigate whether higher [(18)F]FEMPA binding in AD patients than in controls could be detected in vivo.

In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548.

Purpose: A novel [(68)Ga]-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 peptide (BAY86-7548) having high affinity to bombesin receptor subtype II to detect primary and metastatic prostate carcinoma using positron emission tomography/computed tomography (PET/CT) was synthesized and evaluated for prostate cancer.

Experimental Design: In this first human study with BAY86-7548, 14 men scheduled for radical prostatectomy (n = 11) or with biochemical recurrence after surgery or hormonal therapy (n = 3) were enrolled. The patients received an intravenous injection of BAY86-7548 followed by over 60-minute dynamic imaging of prostate gland (n = 10) and/or subsequent whole-body imaging (n = 14).

Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men.

Unlabelled: This first-in-human study investigated the safety, tolerability, metabolism, pharmacokinetics, biodistribution, and radiation dosimetry of (68)Ga-bombesin antagonist (68)Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (BAY 86-7548).

Methods: Five healthy men underwent dynamic whole-body PET/CT after an intravenous injection of BAY 86-7548 (138 ± 5 MBq). Besides total radioactivity, plasma samples were analyzed by radio-high-performance liquid chromatography for metabolism of the tracer.

Minimum intensity projections of the biliary system using 16-channel multidetector computed tomography in patients with biliary obstruction: comparison with MRCP.

The objective was the evaluation of minimum intensity projections (MinIP) of 16-channel multidetector computed tomography (MDCT) data for the visualization of biliary ducts with magnetic resonance cholangiopancreatography (MRCP) as reference method. Twenty-five patients with biliary obstruction who received MDCT of the abdomen and MRCP without subsequent interventions were analysed. Coronal and axial MinIP were reconstructed from the MDCT-data.

Value of axial and coronal maximum intensity projection (MIP) images in the detection of pulmonary nodules by multislice spiral CT: comparison with axial 1-mm and 5-mm slices.

The purpose of this study was to investigate the diagnostic accuracy of non-overlapping 10-mm axial and coronal maximum intensity projections (MIP) in comparison with standard axial 1-mm and 5-mm slices in the detection of pulmonary nodules. Sixty patients with suspected nodules who underwent multislice spiral CT of the chest were evaluated. Axial 1-mm and 5-mm slices as well as non-overlapping 10-mm axial/coronal MIPs were interpreted independently by three blinded radiologists.

Sagittal alignment after anterior debridement and fusion with or without additional posterior instrumentation in the treatment of pyogenic and tuberculous spondylodiscitis.

Study Design: A retrospective clinical study investigated patients undergoing surgery for destructive pyogenic and tuberculous spondylodiscitis.

Objective: To compare anterior debridement and bone grafting with a combined anterior and posterior procedure in terms of the physiologic alignment of the segmental sagittal spinal profile.

Summary Of Background Data: There is considerable agreement in the literature on the indications for surgical treatment of destructive spondylodiscitis.

Peritumoural versus subareolar administration of technetium-99m nanocolloid for sentinel lymph node detection in breast cancer: preliminary results of a prospective intra-individual comparative study.

The scintigraphic detection of sentinel lymph nodes (SNs) in early-stage breast cancer is a widely accepted diagnostic method. However, which radiotracer administration mode should be used is still controversial. This prospective study aimed to intra-individually compare the detection rates obtained after peritumoural versus subareolar injection with regard to SN number and localisation.

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study.

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes.