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Background: Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing Ga-labelled analogues, endoradiotheraphy with Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Methods: Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA and DOTA(MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide Ga and the β emitting nuclide Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. Results: The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed Ga and >98 % with Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [Ga]DOTA (SUV = 5.4 ± 0.6) followed by [F]NaF (SUV = 4.8 ± 0.2), [Ga]DOTA (SUV = 4.5 ± 0.2) and [Ga]BPAPD (SUV = 3.2 ± 0.3). [Lu]DOTA showed a similar distribution as the diagnostic Ga complex. Conclusion: The Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [Ga]DOTA, which makes this compound probably an interesting bone targeting agent for a therapeutic approach with Lu. The therapeutic compound [Lu]DOTA showed a high target-to-background ratio. SPECT experiments showed concordance to the PET scans in healthy rats. [Ga/Lu]DOTA appears to be a potential theranostic combination in the management of disseminated bone metastases. [ABSTRACT FROM AUTHOR]

Laser-driven electron recollision is at the heart of the rapidly growing field of attosecond science. The recollision wavepacket is qualitatively described within the strong-field approximation, which commonly assumes tunnelling ionization and plane-wave propagation of the liberated electron in the continuum. However, with increasing experimental sophistication, refinements to this simple model have become necessary. Through careful modelling and measurements of laser-induced recollision holography using aligned N2 molecules, we demonstrate that the continuum electron wavepacket already carries a non-trivial spatial phase structure immediately following ionization. This effect is of rather general character: any molecule and any non-isotropic system that is ionized by a strong laser field will exhibit an offset in the phase of the continuum electron wavepacket. Specifically, this has important implications for any coherent scattering process in molecules, such as high-harmonic generation or laser-induced electron holography. [ABSTRACT FROM AUTHOR]

At the transition from the gas to the liquid phase of water, a wealth of new phenomena emerge, which are absent for isolated H2O molecules. Many of those are important for the existence of life, for astrophysics and atmospheric science. In particular, the response to electronic excitation changes completely as more degrees of freedom become available. Here we report the direct observation of an ultrafast transfer of energy across the hydrogen bridge in (H2O)2 (a so-called water dimer). This intermolecular coulombic decay leads to an ejection of a low-energy electron from the molecular neighbour of the initially excited molecule. We observe that this decay is faster than the proton transfer that is usually a prominent pathway in the case of electronic excitation of small water clusters and leads to dissociation of the water dimer into two H2O+ ions. As electrons of low energy (∼0.7–20 eV) have recently been found to efficiently break-up DNA constituents, the observed decay channel might contribute as a source of electrons that can cause radiation damage in biological matter. [ABSTRACT FROM AUTHOR]