[PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA]. / PET-CT/-MRT der Prostata : Von 18F-FDG zu 68Ga-PSMA.

CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning.

Preferred orientations and stability of medium length n-alkanes solidified in mesoporous silicon.

The n-alkanes C(16)H(34), C(17)H(36), C(19)H(40), and C(25)H(52) have been imbibed and solidified in mesoporous, crystalline silicon with a mean pore diameter of 10 nm. The structures and phase sequences have been determined by x-ray diffractometry. Apart from a reduction and the hysteresis of the melting-freezing transition, we find a set of six discrete orientation states ("domains") of the confined alkane crystals with respect to the lattice of the silicon host. The growth process responsible for the domain selection is interpreted as a nanoscale version of the Bridgman technique known from single-crystal growth. Oxidation of the pore walls leads to extrusion of the hydrocarbons upon crystallization, whereas the solidified n-alkanes investigated in nonoxidized, porous silicon are thermodynamically stable.

[PSMA-targeted radioligand therapy in prostate cancer]. / Radionuklidtherapie des Prostatakarzinoms mittels PSMA-Lutetium.

Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with ß­radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany. Several retrospective case series demonstrate its activity with a prostate-specific antigen (PSA) decrease >50% in 30-60% of mCRPC patients. The toxicity seems to be low. Hematologic grade 4 toxicity has not been observed and grade 3 toxicities rarely occur. The main nonhematologic adverse events are intermittent dry mouth because of unspecific PSMA expression in the salivary glands as well as fatigue and nausea. Currently there are no prospective studies available for evaluation of PSMA-targeted RLT and a survival benefit over approved standard therapies such as abiraterone, enzalutamide, radium-223-dichloride, docetaxel or cabazitaxel has not been shown. PSMA-targeted RLT should therefore currently only be offered after critical evaluation in patients who exhausted the approved standard therapies.

Structural transformations of even-numbered n-alkanes confined in mesopores.

The n-alkanes C12H26, C14H30, and C16H34 have been imbibed and solidified in mesoporous Vycor glass with a mean pore diameter of 10 nm. The samples have been investigated by x-ray diffractometry and calorimetric measurements. The structures and phase sequences have been determined. Apart from a reduction and the hysteresis of the melting-freezing transition, pore-confined C12 reproduces the liquid-triclinic phase sequence of the bulk material, but for C16 an orthorhombic rotator mesophase appears that in the bulk state is absent for C16 but well known from odd-numbered alkanes of similar length. In pore-confined C14 this phase shows up on cooling but not on heating.

MLN4924 induces Noxa upregulation in acute myelogenous leukemia and synergizes with Bcl-2 inhibitors.

MLN4924 (pevonedistat), an inhibitor of the Nedd8 activating enzyme (NAE), has exhibited promising clinical activity in acute myelogenous leukemia (AML). Here we demonstrate that MLN4924 induces apoptosis in AML cell lines and clinical samples via a mechanism distinct from those observed in other malignancies. Inactivation of E3 cullin ring ligases (CRLs) through NAE inhibition causes accumulation of the CRL substrate c-Myc, which transactivates the PMAIP1 gene encoding Noxa, leading to increased Noxa protein, Bax and Bak activation, and subsequent apoptotic changes. Importantly, c-Myc knockdown diminishes Noxa induction; and Noxa siRNA diminishes MLN4924-induced killing. Because Noxa also neutralizes Mcl-1, an anti-apoptotic Bcl-2 paralog often upregulated in resistant AML, further experiments have examined the effect of combining MLN4924 with BH3 mimetics that target other anti-apoptotic proteins. In combination with ABT-199 or ABT-263 (navitoclax), MLN4924 exerts a synergistic cytotoxic effect. Collectively, these results provide new insight into MLN4924-induced engagement of the apoptotic machinery that could help guide further exploration of MLN4924 for AML.

Aging and memory effects in a clathrate.

The out-of-equilibrium low-frequency complex susceptibility of the orientational glass methanol(73%)-beta-hydroquinone-clathrate is studied using temperature-stop protocols in aging experiments. Although the material does not have a sharp glass transition aging effects including rejuvenation and memory similar to the effects in spin glasses are found at low temperatures.

A geometric centroid principle and its application.

A new concept of approximation for rigid point sets is suggested. As a necessary condition of optimality, the principle of the conjoint centroid is proved: to achieve a best approximation, certain co-sets must conjoin their centroids. The practical use of the centroid principle, and how it opens up a non-classical method of modelling various aspects of orientational disorder in crystals, is demonstrated. The principle is applied to the interpretation of density data, to the prediction of high-pressure conformations through qualitative simulations, and to the prediction and computation of disordered sets of possible reorientation pathways which explain the shape of the electron-density distribution reconstructed from diffraction experiments. It is also demonstrated how an inversion of the centroid principle can be used to model forces between the parts of the disordered structures.

Pattern formation at the bicritical point of the Faraday instability.

We present measurements on parametrically driven surface waves (Faraday waves) performed in the vicinity of a bicritical point in parameter space, where modes with harmonic and subharmonic time dependence interact. The primary patterns are squares in the subharmonic and hexagons in the harmonic regime. If the primary instability is harmonic we observe a hysteretic secondary transition from hexagons to squares without a perceptible variation of the fundamental wavelength. The transition is understood in terms of a set of coupled Landau equations and related to other canonical examples of phase transitions in nonlinear dissipative systems. Moreover, the subharmonic-harmonic mode competition gives rise to a variety of new superlattice states. These structures are interpreted as mediator modes involved in the transition between patterns of fourfold and sixfold rotational symmetry.

Critical adsorption in a well-defined geometry.

A fluid's density profile near a wall is predicted to assume a universal shape near the liquid-vapor critical point, a phenomenon termed critical adsorption. This universal shape is predicted to depend on the boundary conditions of the fluid at the walls and is predicted to be a function of the ratio z/xi, where z is the distance from the wall and xi is the bulk correlation length. A body of evidence confirms the analogous phenomenon of critical adsorption in binary fluids near the critical demixing point, but in the simple liquid-vapor system the experimental situation is not as clear. For example, critical adsorption of SF6 was observed in porous glass for reduced temperature t=T/T(c)-1>10(-3). However, for t<10(-3) a desorption behavior is seen. This desorption has so far resisted rigorous theoretical explanation. We report measurements of the critical adsorption of nitrogen inside a capacitor gap with a simple parallel plate geometry and open gap of 3 microm. Unlike the previous experiments with SF6, the data show a monotonic increase in the adsorption between t=5 x 10(-4) and t=10(-6), consistent with theoretical prediction and without any indication of desorption.

Amplitude measurements of Faraday waves.

A light reflection technique is used to measure quantitatively the surface elevation of Faraday waves. The performed measurements cover a wide parameter range of driving frequencies and sample viscosities. In the capillary wave regime the bifurcation diagrams exhibit a frequency independent scaling proportional to the wavelength. We also provide numerical simulations of the full Navier-Stokes equations, which are in quantitative agreement up to supercritical drive amplitudes of epsilon approximately equal 20%. The validity of an existing perturbation analysis is found to be limited to epsilon<2.5%.

Critical behavior of the frustrated antiferromagnetic six-state clock model on a triangular lattice.

We study the antiferromagnetic six-state clock model with nearest neighbor interactions on a triangular lattice with extensive Monte Carlo simulations. We find clear indications of two phase transitions at two different temperatures: Below T(I) a chirality order sets in and by a thorough finite-size-scaling analysis of the specific heat and the chirality correlation length we show that this transition is in the Ising universality class (with a nonvanishing chirality order parameter below T(I)). At T(KT) (

Phase relaxation of Faraday surface waves.

Surface waves on a liquid-air interface excited by a vertical vibration of a fluid layer (Faraday waves) are employed to investigate the phase relaxation of ideally ordered patterns. By means of a combined frequency-amplitude modulation of the excitation signal a periodic expansion and dilatation of a square wave pattern is generated, the dynamics of which is well described by a Debye relaxator. By comparison with the results of a linear theory, it is shown that the measured relaxation time allows a precise evaluation of the phase diffusion constant.